Small Nuclear Ribonucleoprotein Polypeptide Research Articles

Impact of potential biomarkers, SNRPE, COX7C, and RPS27, on idiopathic Parkinson's disease.

Parkinson's disease (PD) is a progressive neuro-degenerative disorder most common in older adults which is associated with impairments in movement and other body functions. Most PD cases are classified as idiopathic PD (IPD), meaning that the etiology remains unidentified. To identify key genes and molecular mechanisms to identify biomarkers applicable to IPD. We applied a bioinformatics approach using a gene expression in whole blood dataset to pinpoint differentially expressed genes (DEGs) and pathways involved in IPD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of DEGs were subsequently performed. A protein-protein interaction (PPI) network was then constructed to select hub genes that may influence IPD. We further investigated the levels of differentially methylated regions (DMRs) and differentially expressed microRNA (DEMs) of whole blood of patients with IPD to validate hub genes. Additionally, we examined the hub gene expression patterns in the substantia nigra (STN) using single-cell RNA sequencing datasets. In total, we identified 124 DEGs in the blood samples of patients with IPD, with GO and KEGG analyses highlighting their significant enrichment. Analysis of PPI networks revealed three major clusters and hub genes: small nuclear ribonucleoprotein polypeptide E (SNRPE), cytochrome C oxidase subunit 7C (COX7C), and ribosomal protein S27 (RPS27). DMRs and DEMs analyses revealed hub gene regulation via epigenetic and RNA interference. In particular, SNRPE and RPS27 showed identically regulated gene expression in the STN. This study suggests that SNRPE, COX7C, and RPS27 in whole-blood samples derived from patients may be useful biomarkers for IPD.

Small Nuclear Ribonucleoprotein Polypeptides B and B1 Promote Osteosarcoma Progression via Activating the Ataxia-Telangiectasia Mutated Signaling Pathway through Ribonucleotide Reductase Subunit M2

Osteosarcoma is a malignant bone tumor characterized by high metastatic potential and recurrence rates post-therapy. The small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB), a core component of spliceosome, have been reported to exhibit upregulation across several cancer types. However, the precise role of SNRPB in osteosarcoma progression remains poorly elucidated. Herein, we explored SNRPB expression in human osteosarcoma tissues and normal bone tissues by immunohistochemical staining (IHC) staining, revealing a notable upregulation of SNRPB in osteosarcoma, correlating with diminished survival rates. Moreover, the in vitro loss-of-function experiments showed that SNRPB knockdown significantly suppressed the osteosarcoma cell proliferation and migration, as well as tubule formation of HUVECs, while enhancing osteosarcoma cell apoptosis. Mechanistically, we revealed that SNRPB promoted the transcription of ribonucleotide reductase subunit M2 (RRM2) via E2F transcription factor 1 (E2F1). Further rescue experiments indicated that RRM2 was required for SNRPB-induced malignant behaviors in osteosarcoma. Additionally, we confirmed that the function of SNRPB in osteosarcoma cell growth and apoptosis was associated with ATM signaling pathway activation. In conclusion, our findings provide initial insights into the underlying mechanisms governing SNRPB-induced osteosarcoma progression and proposed for SNRPB as a novel therapeutic target in osteosarcoma management.

JAK and STAT5B mediate olfactory response of migratory locusts to their own volatiles

Janus kinase (JAK) and signal transducer and activator of transcription (STAT) signaling affect social aggregation, mood and psychiatric disorders, nociceptive and depressive behaviors. Olfactory dysfunction is one of the distinct symptoms of these behaviors, but function and mechanism of JAK and STAT in modulating olfaction remain largely unknown. Migratory locusts show olfactory preference for their own volatiles. We thus use this animal model to explore functions and mechanisms of JAK and STAT5B in mediating olfaction response to their own volatiles. Tissue distribution study shows that JAK and STAT5B express in antennae and brains, especially in antennal lobes and mushroom bodies in locust brains, and knockdown of these two genes by RNA interference (RNAi) in antennae and brains results in the loss of olfactory preference for locust volatiles, including chemical odorants indole and β-ionone. RNA-seq analysis reveals that JAK and STAT5B RNAi knockdown downregulates a functional class of transcripts in nucleoprotein complex, including heterogeneous nuclear ribonucleoprotein C (hnRNPC) and small nuclear ribonucleoprotein polypeptide F (SNRPF). HnRNPC and SNRPF mRNAs and proteins are also expressed in antennae and brains, and RNAi knockdown of these two genes reduces the percentage of locusts preferring volatiles, including chemical odorants indole and β-ionone. Furthermore, RNAi knockdown of dopamine receptor 1 (DopR1) results in the decrease of JAK mRNA level in antennae, and JAK/STAT5B, hnRNPC and SNRPF are required for dopamine receptor 1 (DopR1) to modulate olfactory preference for their own volatiles. This study confirms that JAK/STAT5B signaling modulates olfaction by affecting expression levels of hnRNPC and SNRPF, and this pathway is also required for DopR1 to modulate olfactory preference for their own volatiles. These findings highlight novel roles of JAK and STAT5B in modulating olfactory preference. This study provides novel insights into functional links among JAK/STAT5B signaling, RNA binding proteins and DopR1 underlying the modulation of olfactory behaviors.

Oncofetal SNRPE promotes HCC tumorigenesis by regulating the FGFR4 expression through alternative splicing.

Due to insufficient knowledge about key molecular events, Hepatocellular carcinoma (HCC) lacks effective treatment targets. Spliceosome-related genes were significantly altered in HCC. Oncofetal proteins are ideal tumor therapeutic targets. Screening of differentially expressed Spliceosome-related oncofetal protein in embryonic liver development and HCC helps discover effective therapeutic targets for HCC. Differentially expressed spliceosome genes were analysis in fetal liver and HCC through bioinformatics analysis. Small nuclear ribonucleoprotein polypeptide E (SNRPE) expression was detected in fetal liver, adult liver and HCC tissues. The role of SNRPE in HCC was performed multiple assays in vitro and in vivo. SNRPE-regulated alternative splicing was recognized by RNA-Seq and confirmed by multiple assays. We herein identified SNRPE as a crucial oncofetal splicing factor, significantly associated with the adverse prognosis of HCC. SOX2 was identified as the activator for SNRPE reactivation. Efficient knockdown of SNRPE resulted in the complete cessation of HCC tumorigenesis and progression. Mechanistically, SNRPE knockdown reduced FGFR4 mRNA expression by triggering nonsense-mediated RNA decay. A partial inhibition of SNRPE-induced malignant progression of HCC cells was observed upon FGFR4 knockdown. Our findings highlight SNRPE as a novel oncofetal splicing factor and shed light on the intricate relationship between oncofetal splicing factors, splicing events, and carcinogenesis. Consequently, SNRPE emerges as a potential therapeutic target for HCC treatment. Model of oncofetal SNRPE promotes HCC tumorigenesis by regulating the AS of FGFR4 pre-mRNA.

A new tandem repeat-enriched lncRNA XLOC_008672 promotes gastric carcinogenesis by regulating G3BP1 expression.

Aberrant expression of forkhead box transcription factor 1 (FOXM1) plays critical roles in a variety of human malignancies and predicts poor prognosis. However, little is known about the crosstalk between FOXM1 and long noncoding RNAs (lncRNAs) in tumorigenesis. The present study identifies a previously uncharacterized lncRNA XLOC_008672 in gastric cancer (GC), which is regulated by FOXM1 and possesses multiple copies of tandem repetitive sequences. LncRNA microarrays are used to screen differentially expressed lncRNAs in FOXM1 knockdown GC cells, and then the highest fold downregulation lncRNA XLOC_008672 is screened out. Sequence analysis reveals that the new lncRNA contains 62 copies of 37-bp tandem repeats. It is transcriptionally activated by FOXM1 and functions as a downstream effector of FOXM1 in GC cells through invitro and invivo functional assays. Elevated expression of XLOC_008672 is found in GC tissues and indicates worse prognosis. Mechanistically, XLOC_008672 can bind to small nuclear ribonucleoprotein polypeptide A (SNRPA), thereby enhancing mRNA stability of Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) and, consequently, facilitating GC cell proliferation and migration. Our study discovers a new uncharacterized lncRNA XLOC_008672 involved in GC carcinogenesis and progression. Targeting FOXM1/XLOC_008672/SNRPA/G3BP1 signaling axis might be a promising therapeutic strategy for GC.

Abstract 5141: Autoantibody profiling for predictive biomarkers for immune-related adverse events and clinical benefit in rare tumors treated with anti-PD-1 therapy

Abstract Background: Immune checkpoint inhibitors (ICIs) have changed the cancer treatment paradigm; however, with high frequency of immune-related adverse events (irAEs) and limited response rates in select patients. This underscores the unmet need for the development of biomarkers predictive for the development of irAEs and ICI response. Herein, we conducted autoantibody (AAb) profiling to assess baseline (BL) AAb associations with clinical benefit (CB) and irAEs in patients (pts) with rare tumors (RT) treated with programmed cell death protein 1 (anti-PD-1) therapy. Methods: AAbs against 1168 antigens were analyzed using the SeroTag antibody discovery technology. The study included 41 pts with RT who received anti-PD-1 therapy. We conducted a Significance Analysis of Microarray (SAM) to analyze the association between BL AAbs with irAEs and CB (defined as pts achieving complete response (CR), partial response (PR), or stable disease (SD) for ≥4 months by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1). AAb biomaker candidates were discovered based on filtering for SAM hits with p < 0.05 and a delta score |D| >2. Results: Table 1 outlines patients’ demographics. CB and irAEs were observed in 34% and 39% of patients, respectively. Eighteen BL AAbs were significantly associated with CB such as DNA ligase III (LIG3) and small nuclear ribonucleoprotein polypeptide (SNRPA) (p = 0.002 and p = 0.003, respectively). Likewise, 13 BL AAbs showed significant associations with any-grade irAEs, particularly AAbs to breast cancer 2 (BRCA2) DNA repair associated antigen and chromatin-modifying protein 4A (CHMP4A) (p = 0.001 and p = 0.003, respectively). Conclusion: The predictive potential of autoantibodies as biomarkers is promising. Further evaluation in larger cohorts is needed for validation of our findings and understanding the underlying mechanism. Table 1. Patients’ demographics Total patients n=41 Median age in years (range) 66 (35-84) Male n=19 Female n=22 Tumor type Carcinoma of unknown primary n=13 Squamous cell carcinoma of the skin n=9 Small cell malignancies of non-pulmonary origin n=7 Adrenocortical carcinoma n=6 Vascular sarcoma n=5 Other rare histology n=1 Clinical benefit CR, PR, or SD ≥ 4 months n=14 SD <4 months or progressive disease (PD) n=23 Not evaluable n=4 irAEs Yes n=16 No n=25 Citation Format: Mohamed H. Derbala, Joud Hajjar, Bettzy Stephen, Serdar A. Gurses, Evan Kwiatkowski, Petra Budde, Hans-Dieter Zucht, Manuel Bräutigam, Ann-Sophie Schubert, Behnaz Ahangarianabhari, Enedelia Rodriguez, Mohamed Gouda, Lilibeth Castillo, Abdulrazzak Zarifa, Jeffrey A. How, Justin T. Moyers, David S. Hong, Funda Meric-Bernstam, Aung Naing. Autoantibody profiling for predictive biomarkers for immune-related adverse events and clinical benefit in rare tumors treated with anti-PD-1 therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5141.

Does Sperm SNRPN Methylation Change with Fertility Status and Age? A Systematic Review and Meta-Regression Analysis.

Background: The Small Nuclear Ribonucleoprotein Polypeptide N (SNRPN) gene is a paternally expressed imprinted gene, whose abnormal methylation appears to be associated with syndromes associated with the use of assisted reproductive techniques (ART), such as Angelman and Prader-Willi. Data present in the literature suggest the association between aberrant sperm SNRPN gene methylation and abnormal sperm parameters. The latest meta-analysis on the methylation pattern of this gene in spermatozoa of infertile patients published in 2017 reported a higher degree of methylation in the spermatozoa of infertile patients compared to fertile controls. Objectives: Here we provide an updated and comprehensive systematic review and meta-analysis of the sperm methylation pattern of the SNRPN gene in patients with abnormal sperm parameters/infertility compared to men with normal sperm parameters/fertile. For the first time in the literature, we performed a meta-regression analysis to evaluate whether age or sperm concentration could influence the methylation status of this gene at the sperm level. Methods: This meta-analysis was registered in PROSPERO (n. CRD42023397056). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) and the MOOSE guidelines for meta-analyses and systematic reviews of observational studies were strictly followed in our meta-analysis. According to our Population Exposure Comparison Outcome (PECO) question, we included data from original articles assessing the levels of SNRPN gene methylation at the sperm level in infertile patients or patients with abnormalities in one or more sperm parameters compared to fertile or normozoospermic men. Results: Only six of 354 screened studies were included in the quantitative synthesis. Our analysis showed significantly higher levels of SNRPN gene methylation in patients compared to controls. However, significant heterogeneity was found between studies. In sensitivity analysis, no studies were sensitive enough to skew the results. The Egger test showed no publication bias. In the meta-regression analysis, the results were independent of age and sperm concentration in the overall population. The same results were found in the control group. However, when analyzing the patient group, a direct correlation was found between SNRPN methylation and age, indicating that the degree of methylation of the SNRPN gene increases with advancing age. Conclusions: Fertility status or abnormality of sperm parameters is associated with a change in the methylation pattern of the SNRPN gene, with higher levels found in infertile patients or those with abnormal sperm parameters compared to fertile men or men with normal sperm parameters. In the group of infertile patients/patients with abnormal sperm parameters, age was directly correlated to the degree of SNRPN methylation, highlighting the presence of a mechanism that explains the age-related altered sperm quality and the risk of ART. Despite some limitations present in the analyzed studies, our results support the inclusion of SNRPN methylation in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to analyze in couples who want to undergo ART.

Assessing the Interactive Effects of High Salinity and Stocking Density on the Growth and Stress Physiology of the Pacific White Shrimp Litopenaeus vannamei

This study was conducted to evaluate the effects of high salinity combined with stocking density on Litopenaeus vannamei. Three salinity gradients, namely, 28 g/L, 36 g/L, and 44 g/L, and two stocking densities, namely, 300 and 600 shrimp/m3, were used to analyze the synergistic effect of high salinity and stocking density on the growth performance, digestibility, and energy budgets of L. vannamei. The experimental testing period lasted 45 days. The research results showed that a salinity level of 36 g/L was the most suitable salinity level for shrimp growth under both high and low stocking densities. The body weight, specific growth rate, and relative weight gain of the shrimp in the 36 g/L salinity group were significantly higher than those in the other two salinity groups under both high and low stocking densities. The high-density farming group with 600 shrimp/m3 exhibited a significant inhibition of shrimp growth compared to the low-density group under the same salinity conditions. The activities of amylase, lipase, and protease in the high-density-group shrimp gradually decreased with an increase in salinity, and the three digestive enzymes had the same overall effect of changing trends. This indicates that under high-density farming conditions, the increase in salinity is not conducive to the digestive function of shrimps. At the same time, the proportion of respiratory energy to feeding energy gradually decreased in the high-density group and with the increase in salinity. However, under the same salinity conditions, the higher the stocking density, the higher the energy consumed by respiration compared to the low-density group. In addition, the expression of the growth-related gene’s small nuclear ribonucleoprotein polypeptide G (SNRPG) under high stocking density was significantly lower than that in the low-density group at a salinity of 28 g/L, and ribosomal protein L7 (RPL7) expression was also significantly lower under high stocking density than that in the low-density group at a salinity of 44 g/L. The expression levels of molting-related genes retinoid X receptor (RXR), ecdysone receptor (ECR), and ecdysone-induced protein 75 (E75) were significantly higher in the 36 g/L salinity group compared with the other two salinity groups under high-stocking-density treatment. The findings indicate that the synergistic effects of salinity and stocking density have a significant impact on the growth of L. vannamei, and excessive salinity would inhibit its growth in the process of high-density culturing.

SNRPB promotes the progression of hepatocellular carcinoma via regulating cell cycle, oxidative stress, and ferroptosis.

Small Nuclear Ribonucleoprotein Polypeptides B and B1 (SNRPB) have been linked to multiple human cancers. However, the mechanism of SNRPB in hepatocellular carcinoma (HCC) and whether SNRPB has a synergistic effect with sorafenib in the treatment of HCC remain unclear. In this study, bioinformatic analysis found that SNRPB was an independent prognostic factor for HCC that exerted a critical effect on the progression of HCC. SNRPB was linked with immune checkpoints, cell cycle, oxidative stress and ferroptosis in HCC. Single cell sequencing analysis found that HCC cell subset with high expression of SNRPB, accounted for a higher proportion in HCC cells with higher stages, had higher expression levels of the genes which promote cell cycle, inhibit oxidative stress and ferroptosis, and had higher cell cycle score, lower oxidative stress score and ferroptosis score. Single-sample gene set enrichment analysis (ssGSEA) analysis found that 17 oxidative stress pathways and 68 oxidative stress-ferroptosis related genes were significantly correlated with SNRPB risk scores. SNRPB knockdown induced cell cycle G2/M arrest and restrained cell proliferation, while downregulated the expression of CDK1, CDK4, and CyclinB1. The combined treatment (SNRPB knockdown+sorafenib) significantly inhibited tumor growth. In addition, the expression of SLC7A11, which is closely-related to ferroptosis, decreased significantly in vitro and in vivo. Therefore, SNRPB may promote HCC progression by regulating immune checkpoints, cell cycle, oxidative stress and ferroptosis, while its downregulation inhibits cell proliferation, which enhances the therapeutic effect of sorafenib, providing a novel basis for the development of HCC therapies.

Upregulated enhancer of rudimentary homolog promotes epithelial‑mesenchymal transition and cancer cell migration in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the deadliest cancers regarding both mortality rate and number of deaths and warrants greater effort in the development of potential therapeutic targets. The enhancer of rudimentary homolog (ERH) has been implicated in the promotion and progression of certain types of cancer. In the present study, ERH was assessed for its expression pattern and survival association with LUAD in public transcriptomic and proteomic databases. Bioinformatic methods and data from websites, including University of Alabama at Birmingham CANcer data analysis Portal and The Cancer Genome Atlas, were utilized to demonstrate the functional behaviors and corresponding pathways of ERH in LUAD. Human A549 and CL1‑0 cell lines were used to validate the findings via functional assays. It was demonstrated that the expression of ERH, at both the transcriptomic and proteomic levels, was higher in LUAD compared with in adjacent non‑tumor lung tissue and was associated with worse survival prognosis. Moreover, high ERH expression was correlated with more aggressive functional states, such as cell cycle and invasion in LUAD, and the positive ERH‑correlated gene set was associated with worse survival and an immunosuppressive tumor microenvironment. Small nuclear ribonucleoprotein polypeptide G was identified as a molecule that potentially interacted with ERH. Lastly, it was demonstrated that ERH promoted epithelial‑mesenchymal transition and cell migration invitro, but not proliferation. In conclusion, higher expression of ERH in LUAD may facilitate cancer progression and confer worse outcomes. Further deep investigation into the role of ERH in LUAD is needed.

LINC00461 Knockdown Enhances the Effect of Ixazomib in Multiple Myeloma Cells.

LINC00461 has been implicated to be involved in several types of cancer while its roles in multiple myeloma remain unclear. Our study aims to investigate the roles of LINC00461 in multiple myeloma and explore its effects on ixazomib therapy. LINC00461 and small nuclear ribonucleoprotein polypeptide (SNRP) B2 knockdown stable cell lines were constructed. Cell viability assays including MTT, cell number counting, and colony formation were performed. RNA-pull down and immunoblotting assays were conducted to determine the intramolecular interactions. qRT-PCR and western blotting were conducted to determine the levels of target genes. Kaplan-Meier analysis was used to evaluate overall survival rates. Knockdown of LINC00461 or SNRPB2 enhanced ixazomib's cytotoxicity, as well as affected its regulatory effects on cell apoptosis and cell cycle distribution. Further results showed that LINC00461 knockdown reduced the expression levels of SNRPB2 by their interactions. Additionally, a positive correlation between LINC00461 and SNRPB2 was found in patients with multiple myeloma. Low expression of SNRPB2 was associated with a high survival rate in patients with multiple myeloma. Knockdown of LINC00461 enhanced the therapeutic effects of ixazomib against multiple myeloma in part by the regulation of SNRPB2.

Defects of the spliceosomal gene SNRPB affect osteo- and chondro-differentiation.

Although gene splicing occurs throughout the body, the phenotype of spliceosomal defects is largely limited to specific tissues. Cerebro-costo-mandibular syndrome (CCMS) is one such spliceosomal disease, which presents as congenital skeletal dysmorphism and is caused by mutations of SNRPB gene encoding Small Nuclear Ribonucleoprotein Polypeptides B/B' (SmB/B'). This study employed in vitro cell cultures to monitor osteo- and chondro-differentiation and examined the role of SmB/B' in the differentiation process. We found that low levels of SmB/B' by knockdown or mutations of SNRPB led to suppressed osteodifferentiation in Saos-2 osteoprogenitor-like cells, which was accompanied by affected splicing of Dlx5. On the other hand, low SmB/B' led to promoted chondrogenesis in HEPM mesenchymal stem cells. Consistent with other reports, osteogenesis was promoted by the Wnt/β-catenin pathway activator and suppressed by Wnt and BMP blockers, whereas chondrogenesis was promoted by Wnt inhibitors. Suppressed osteogenic markers by SNRPB knockdown were partly rescued by Wnt/β-catenin pathway activation. Reporter analysis revealed that suppression of SNRPB results in attenuated Wnt pathway and/or enhanced BMP pathway activities. SNRPB knockdown altered splicing of TCF7L2 which impacts Wnt/β-catenin pathway activities. This work helps unravel the mechanism underlying CCMS whereby reduced expression of spliceosomal proteins causes skeletal phenotypes.

N-Acetylglucosamine Kinase-Small Nuclear Ribonucleoprotein Polypeptide N Interaction Promotes Axodendritic Branching in Neurons via Dynein-Mediated Microtubule Transport.

N-acetylglucosamine kinase (NAGK) has been identified as an anchor protein that facilitates neurodevelopment with its non-canonical structural role. Similarly, small nuclear ribonucleoprotein polypeptide N (SNRPN) regulates neurodevelopment and cognitive ability. In our previous study, we revealed the interaction between NAGK and SNRPN in the neuron. However, the precise role in neurodevelopment is elusive. In this study, we investigate the role of NAGK and SNRPN in the axodendritic development of neurons. NAGK and SNRPN interaction is significantly increased in neurons at the crucial stages of neurodevelopment. Furthermore, overexpression of the NAGK and SNRPN proteins increases axodendritic branching and neuronal complexity, whereas the knockdown inhibits neurodevelopment. We also observe the interaction of NAGK and SNRPN with the dynein light-chain roadblock type 1 (DYNLRB1) protein variably during neurodevelopment, revealing the microtubule-associated delivery of the complex. Interestingly, NAGK and SNRPN proteins rescued impaired axodendritic development in an SNRPN depletion model of Prader-Willi syndrome (PWS) patient-derived induced pluripotent stem cell neurons. Taken together, these findings are crucial in developing therapeutic approaches for neurodegenerative diseases.

BG01 Confirming small nuclear ribonucleoprotein polypeptide E as a cause of nonsyndromic hypotrichosis

Abstract Hereditary nonsyndromic hypotrichosis comprises at least 15 genetically distinct but phenotypically overlapping disorders. Affected individuals generally have hair at birth, which sheds during infancy or childhood. Severity ranges from partial alopecia to complete loss of scalp and body hair, with phenotypic variability between and within families. Genetic testing is essential for accurate diagnosis and counselling. We describe a case where several factors contributed to a delay in genetic diagnosis. A female child of nonconsanguineous White parents was born at term with normal hair that started to shed at 2 weeks of age. By 6 weeks of age, there was a complete absence of scalp, eyelash and eyebrow hair. There was no relevant family history apart from atopy. On examination at 3.3 years of age, she had total alopecia apart from some hairs in the external auditory canals. Nails, teeth and sweating were normal. She appeared developmentally normal and healthy apart from mild eczema with persistent erythema on both cheeks. The differential diagnosis included autoimmune alopecia and genetic nonsyndromic hypotrichosis. She was recruited to the 100 000 Genomes Project, but primary analysis did not identify any causative variants. Reanalysis using a limited gene-agnostic approach identified heterozygosity for the c.1A>G; p.(Met1?) variant in small nuclear ribonucleoprotein polypeptide E (SNRPE) that was not present in parents. This variant is not present in the gnomAD population database and is predicted to alter the initiation codon of SNRPE. It has been reported de novo in a British girl with sparse scalp hair and eyelashes and absent eyebrows, and in eight affected members of a Spanish family whose phenotypes ranged from sparse eyebrows and eyelashes to complete alopecia (Pasternack SM, Refke M, Paknia E et al. Mutations in SNRPE, which encodes a core protein of the spliceosome, cause autosomal dominant hypertrichosis simplex. Am J Hum Genet 2013; 92:81–7). This condition has been designated hypotrichosis type 11. SNRPE encodes a core protein of U small nuclear ribonucleoproteins, which are essential to the removal of introns from pre-mRNA and thus critical for the post-transcriptional modification of RNA. In our case, review of the primary analysis showed that the incorrect gene panel was applied (‘familial cicatricial alopecia’ instead of ‘nonsyndromic hypotrichosis’) and that SNRPE was listed as ‘amber’ for hypotrichosis, meaning ‘moderate evidence for this gene–disease association and should not yet be used for genome interpretation’. Genomics England has now incorporated nonsyndromic hypotrichosis into the ‘ectodermal dysplasia’ panel, with SNRPE now listed as ‘green’ for hypotrichosis 11, meaning a ‘high level of evidence for this gene–disease association’. This case emphasizes the importance of revisiting negative results as knowledge evolves.

The In Vitro Evaluation of Rooster Semen Pellets Frozen with Dimethylacetamide.

Sperm cryopreservation is an effective technique for conserving animal genetic diversity and transmitting superior genetic backgrounds, maintained via a non-invasive sampling and collection of huge quantities of sperm. Nevertheless, cryopreservation in avian species is not commercially viable because of the rooster sperm's susceptibility to damage. This study aims to estimate the impact of dimethylacetamide (DMA) as a cryoprotectant at different levels (3%, 6%, or 9%) on the post-thawed sperm quality, motility, antioxidant-biomarkers, and the expression of anti-freeze related genes. Semen samples were collected twice a week from twelve roosters aged 40 wk, weighing 3400 ± 70 g, and belonging to the Cairo-B2 chicken strain. Fresh semen samples were rapidly appraised, pooled, diluted with two volumes of a basic extender, and divided equally into three groups. The diluted groups were chilled at -20 °C for 7 min, then gently supplemented with 3, 6, or 9% pre-cooled DMA and equilibrated at 5 °C for a further 10 min. Semen pellets were formed by pipetting drops 7 cm above liquid nitrogen (LN2), which were then kept inside cryovials in the LN2. Thawing was performed 2 months later by taking 3-4 pellets of the frozen semen into a glass tube and warming it in a water bath for 8 s at 60 °C. The results showed that 3% DMA increased the proportion of total motile sperm, progressivity, viability, and plasma membrane integrity (%) compared to the 6% and 9% DMA groups. The lipid peroxidation and antioxidant enzyme activity were improved in the 3% group. At the same time, some anti-freeze-related genes' (including ras homolog family member A (RHOA), heat shock protein 70 (HSP70), and small nuclear ribonucleoprotein polypeptide A (SNRPA1)) expressions were upregulated within the 3% DMA group relative to other groups. In conclusion, the 3% DMA group maintained higher post-thawed sperm quality than the other tested groups.

Identification of a Methylation Pattern in the SNRPN Gene Promoter and its Association with Semen Abnormality Among Iraqi Males

Infertility considered as a multifactorial condition; the small nuclear ribonucleoprotein polypeptide N (SNRPN) gene is an imprinted gene. However, abnormal imprinting of this gene due to the methylation may result in abnormal function or silencing of the gene. Main aim of this study is to investigate the methylation present at the promoter of (SNRPN) gene and its role as a risk factor for male infertility. Sixty- three infertile males with age mean (32.28 ± 6.88 years) and 13 fertile males as a control age mean (34.07 ± 6.52 years) were investigated. Whole genomic DNA was extracted, DNA integrity was checked using β-globin gene as an internal control. The targeted region was amplified by polymerase chain reaction (PCR) technique. In addition, the SNRPN gene's promoter methylation was qualitatively detected using Real time polymerase chain reaction (qPCR) utilizing two sets of primers: methylated and un-methylated. Results reveled that all of the 63 infertile males were experiencing decrease in sperm concentration 9.42 ± 8.70 million/ml, reduced progressive motility 2.89 ± 5.45% as well as strange sperm morphology 27.06 ± 16.50%, while the values in the control group are normal. The results of the current investigation showed that the promoter of SNRPN was hypermethylated in some samples 22.7%, somewhat methylated in others 20.4%, and unmethylated in other samples 56.8% from infertile samples, while none of the 13 control samples had any methylation. These findings suggest that SNRPN gene may be associated with the negative changes in semen parameters, which could lead to male infertility.

Splicing factor SNRPA associated with microvascular invasion promotes hepatocellular carcinoma metastasis through activating NOTCH1/Snail pathway and is mediated by circSEC62/miR-625-5p axis.

Microvascular invasion (MVI) is a crucial risk factor related to the metastasis of hepatocellular carcinoma (HCC), but the underlying mechanisms remain to be revealed. Characterizing the inherent mechanisms of MVI may aid in the development of effective treatment strategies to improve the prognosis of HCC patients with metastasis. Through the Gene Expression Omnibus (GEO) database, we identified that small nuclear ribonucleoprotein polypeptide A (SNRPA) was related to MVI in HCC. SNRPA was overexpressed in MVI-HCC and correlated with poor patient survival. Mechanistically, SNRPA promoted the epithelial-mesenchymal transition (EMT)-like process for HCC cells to accelerate metastasis by activating the NOTCH1/Snail pathway in vitro and in vivo. Importantly, circSEC62 upregulated SNRPA expression in HCC cells via miR-625-5p sponging. Taking these results together, our study identified a novel regulatory mechanism among SNRPA, miR-625-5p, circSEC62 and the NOTCH1/Snail pathway in HCC, which promoted metastasis of HCC and may provide effective suggestions for improving the prognosis of HCC patients with metastasis.

SNRPB promotes cell cycle progression in thyroid carcinoma via inhibiting p53.

Papillary thyroid carcinoma (PTC) accounts for more than 80% of all thyroid carcinoma cases. Small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB) has been indicated to be carcinogenic in several cancers; however, its function and mechanism in PTC are unclarified. Real time quantitative polymerase chain reaction and western blotting revealed the upregulation of SNRPB and downregulation of tumor protein p53 in PTC tissues compared with the normal tissues. Flow cytometry and western blotting displayed that SNRPB silencing induced cell cycle arrest at G1 phase and suppressed the expression levels of Cyclin family proteins in PTC cells. In vivo experiments suggested that SNRPB silencing inhibited PTC tumor growth in mice. Bioinformatics analysis revealed that the expression of SNRPB and cell cycle-associated genes in thyroid carcinoma tissues is positively correlated. Immunofluorescence staining and co-immunoprecipitation demonstrated that SNRPB directly interacted with p53 and suppressed its expression in PTC cells. In conclusion, SNRPB facilitates cell cycle progression in PTC by inhibiting p53 expression.

The oncogenic role of SNRPB in human tumors: A pan-cancer analysis.

Purpose: The purpose of this study was to explore the oncogenic role of small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB) in human tumors. Materials and methods: Study cases were acquired from The Cancer Genome Atlas database, the Gene Expression Omnibus database, The Human Protein Atlas, and the Clinical Proteomic Tumor Analysis Consortium. We then used the R package and several online tools to analyze and visualize the role of SNRPB across tumors. Results: We found that the expression of SNRPB was significantly increased in 28 of 33 tumors, and higher expression was observed in late pathological and TNM stages. Significantly decreased levels of SNRPB promoter methylation were observed in 12 tumors. SNRPB was found to be a risk factor for decreased overall survival in 10 tumors (p < 0.05), a risk factor for decreased disease-specific survival in 8 tumors (p < 0.05), and a risk factor for decreased progression-free interval in 7 tumors (p < 0.05). The PPI network of SNRPB and the top 100 coexpressed genes revealed that CDK1, CDC6, AURKB, CCNB1, CCNA2, and CDC45 were the most closely interacting genes across tumors. The GO and KEGG enrichment analyses revealed that SNRPB and the above genes were mainly enriched with respect to functions in cell cycle-related genetic material replication, assembly, and distribution. SNRPB was significantly associated with immune cell infiltration and the expression of immunomodulation-related genes in several but not all tumors. Conclusion and limitations: The expression of SNRPB was significantly elevated in almost all tumors, and the decreased promoter methylation level may contribute to the elevated expression of SNRPB. SNRPB may facilitate the progression of pathological and TNM stages and is a risk factor for unfavorable prognosis across tumors. However, our research was based on data obtained from public databases, without further validation of our findings at the cellular and animal levels. Therefore, further studies are needed to clarify the oncogenic mechanism of SNRPB and its potential as a therapeutic target.

Non-ubiquitous expression of core spliceosomal protein SmB/B' in chick and mouse embryos.

Although splicing is an integral part of the expression of many genes in our body, genetic syndromes with spliceosomal defects affect only specific tissues. To help understand the mechanism, we investigated the expression pattern of a core protein of the major spliceosome, SmB/B' (Small Nuclear Ribonucleoprotein Polypeptides B/B'), which is encoded by SNRPB. Loss-of-function mutations of SNRPB in humans cause cerebro-costo-mandibular syndrome (CCMS) characterized by rib gaps, micrognathia, cleft palate, and scoliosis. Our expression analysis focused on the affected structures as well as non-affected tissues, using chick and mouse embryos as model animals. Embryos at young stages (gastrula) showed ubiquitous expression of SmB/B'. However, the level and pattern of expression became tissue-specific as differentiation proceeded. The regions relating to CCMS phenotypes such as cartilages of ribs and vertebrae and palatal mesenchyme express SmB/B' in the nucleus sporadically. However, cartilages that are not affected in CCMS also showed similar expressions. Another spliceosomal gene, SNRNP200, which mutations cause retinitis pigmentosa, was also prominently expressed in cartilages in addition to the retina. The expression of SmB/B' is spatiotemporally regulated during embryogenesis despite the ubiquitous requirement of the spliceosome, however, the expression pattern is not strictly correlated with the phenotype presentation.