Function Of Non-coding RNAs Research Articles

The lncRNA Snhg11, a new candidate contributing to neurogenesis, plasticity, and memory deficits in Down syndrome.

Down syndrome (DS) stands as the prevalent genetic cause of intellectual disability, yet comprehensive understanding of its cellular and molecular underpinnings remains limited. In this study, we explore the cellular landscape of the hippocampus in a DS mouse model, the Ts65Dn, through single-nuclei transcriptional profiling. Our findings demonstrate that trisomy manifests as a highly specific modification of the transcriptome within distinct cell types. Remarkably, we observed a significant shift in the transcriptomic profile of granule cells in the dentate gyrus (DG) associated with trisomy. We identified the downregulation of a specific small nucleolar RNA host gene, Snhg11, as the primary driver behind this observed shift in the trisomic DG. Notably, reduced levels of Snhg11 in this region were also observed in a distinct DS mouse model, the Dp(16)1Yey, as well as in human postmortem brain tissue, indicating its relevance in Down syndrome. To elucidate the function of this long non-coding RNA (lncRNA), we knocked down Snhg11 in the DG of wild-type mice. Intriguingly, this intervention alone was sufficient to impair synaptic plasticity and adult neurogenesis, resembling the cognitive phenotypes associated with trisomy in the hippocampus. Our study uncovers the functional role of Snhg11 in the DG and underscores the significance of this lncRNA in intellectual disability. Furthermore, our findings highlight the importance of DG in the memory deficits observed in Down syndrome.

Bioinformatics Applications in Chronic Diseases: A Comprehensive Review of Genomic, Transcriptomics, Proteomic, Metabolomics, and Machine Learning Approaches

This manuscript provides a detailed exploration of the pivotal role that bioinformatics plays in elucidating the intricate molecular landscape associated with chronic diseases. Emphasizing the significance and prevalence of these enduring health issues, the introduction establishes the broader context of bioinformatics in chronic disease research. This review systematically covers the application of bioinformatics tools and techniques in comprehending, identifying, and managing chronic illnesses. The first section highlights the importance of genetics and genomics, detailing the utilization of genomic data and advancements in genetic biomarker discovery. Subsequently, the discussion extends to transcriptomics and gene expression, encompassing profiling methods, the identification of dysregulated genes, and the regulatory functions of non-coding RNA in long-term illnesses.Moving forward, the manuscript delves into proteomics, elucidating protein-protein interaction networks, associated tools and techniques, and post-translational modifications. This comprehensive coverage aims to provide readers with a nuanced understanding of the molecular complexities underlying chronic diseases. The subsequent section focuses on metabolomics and metabolic pathways, with an emphasis on the clinical utility of metabolite biomarkers, changes in metabolic pathways, and techniques for characterizing diseases. Following this, the manuscript explores machine learning applications in bioinformatics, providing insights into their role in enhancing our understanding of chronic diseases. The later part of the manuscript addresses practical applications and case studies, showcasing disease-specific bioinformatics tools, databases, and the broader utility of research findings. Additionally, the penultimate section examines privacy, ethical considerations, and data quality concerns, addressing challenges and potential paths for the field of bioinformatics. In conclusion, the manuscript discusses forthcoming trends and prospective research directions, contributing to the advancement of bioinformatics research in chronic illnesses. Overall, this review provides a comprehensive overview of the multifaceted applications of bioinformatics in chronic disease research.

Non-coding RNAs and angiogenesis in cardiovascular diseases: a comprehensive review.

Non-coding RNAs (ncRNAs) have key roles in the etiology of many illnesses, including heart failure, myocardial infarction, stroke, and in physiological processes like angiogenesis. In transcriptional regulatory circuits that control heart growth, signaling, and stress response, as well as remodeling in cardiac disease, ncRNAs have become important players. Studies on ncRNAs and cardiovascular disease have made great progress recently. Here, we go through the functions of non-coding RNAs (ncRNAs) like circular RNAs (circRNAs), and microRNAs (miRNAs) as well as long non-coding RNAs (lncRNAs) in modulating cardiovascular disorders.

PERFUMES: pipeline to extract RNA functional motifs and exposed structures.

Up to 75% of the human genome encodes RNAs. The function of many non-coding RNAs relies on their ability to fold into 3D structures. Specifically, nucleotides inside secondary structure loops form non-canonical base pairs that help stabilize complex local 3D structures. These RNA 3D motifs can promote specific interactions with other molecules or serve as catalytic sites. We introduce PERFUMES, a computational pipeline to identify 3D motifs that can be associated with observable features. Given a set of RNA sequences with associated binary experimental measurements, PERFUMES searches for RNA 3D motifs using BayesPairing2 and extracts those that are over-represented in the set of positive sequences. It also conducts a thermodynamics analysis of the structural context that can support the interpretation of the predictions. We illustrate PERFUMES' usage on the SNRPA protein binding site, for which the tool retrieved both previously known binder motifs and new ones. PERFUMES is an open-source Python package (https://jwgitlab.cs.mcgill.ca/arnaud_chol/perfumes).

Frontiers and Challenges of Computing ncRNAs Biogenesis, Function and Modulation.

Non-coding RNAs (ncRNAs), generated from nonprotein coding DNA sequences, constitute 98-99% of the human genome. Non-coding RNAs encompass diverse functional classes, including microRNAs, small interfering RNAs, PIWI-interacting RNAs, small nuclear RNAs, small nucleolar RNAs, and long non-coding RNAs. With critical involvement in gene expression and regulation across various biological and physiopathological contexts, such as neuronal disorders, immune responses, cardiovascular diseases, and cancer, non-coding RNAs are emerging as disease biomarkers and therapeutic targets. In this review, after providing an overview of non-coding RNAs' role in cell homeostasis, we illustrate the potential and the challenges of state-of-the-art computational methods exploited to study non-coding RNAs biogenesis, function, and modulation. This can be done by directly targeting them with small molecules or by altering their expression by targeting the cellular engines underlying their biosynthesis. Drawing from applications, also taken from our work, we showcase the significance and role of computer simulations in uncovering fundamental facets of ncRNA mechanisms and modulation. This information may set the basis to advance gene modulation tools and therapeutic strategies to address unmet medical needs.

Long Non-Coding RNAs as Regulators for Targeting Breast Cancer Stem Cells and Tumor Immune Microenvironment: Biological Properties and Therapeutic Potential.

Breast cancer stem cells (BCSCs) is a subpopulation of cancer cells with self-renewal and differentiation capacity, have been suggested to give rise to tumor heterogeneity and biologically aggressive behavior. Accumulating evidence has shown that BCSCs play a fundamental role in tumorigenesis, progression, and recurrence. The development of immunotherapy, primarily represented by programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors, has greatly changed the treatment landscape of multiple malignancies. Recent studies have identified pervasive negative associations between cancer stemness and anticancer immunity. Stemness seems to play a causative role in the formation of cold tumor immune microenvironment (TIME). The multiple functions of long non-coding RNAs (lncRNAs) in regulating stemness and immune responses has been recently highlighted in breast cancer. The review focus on lncRNAs and keys pathways involved in the regulation of BCSCs and TIME. Potential clinical applications using lncRNAs as biomarkers or therapies will be discussed.

Tumor Promoting Effect of Long Non-Coding RNA RP11-556E13.1 and its Clinical Significance in Hepatocellular Carcinoma.

The aim of this study was to reveal the function of the long non-coding RNA (lncRNA) RP11-556E13.1 (RP11) and its clinical significance in hepatocellular carcinoma (HCC). LncRNA and mRNA expression profiling was performed using lncRNA and mRNA microarrays in HCC and adjacent tissues. Human tissue samples were analyzed by semiquantitative real-time polymerase chain reaction (sqRT-PCR) to evaluate the expression of RP11. Smart silencer RNA (siRNA) was used to knockdown the expression of RP11 in HCC cells. The function of RP11 was determined by some cell function experiments in HCC cells. Western blotting (WB) was performed to detect proteins that were presumably associated with these function changes. An Affymetrix Human HTA2.0 microarray was used to detect the underlying mechanism of RP11 in HCC. lncRNA RP11 was the most significantly upregulated lncRNA in HCC tissues compared with the adjacent tissues (p < 0.05, fold change = 20.24). The expression of RP11 was significantly higher in HCC tissues compared to adjacent tissues in 112 tissue pairs (p < 0.05). The higher the expression of RP11 in HCC tissues, the bigger the tumor size, the poorer the histological differentiation, and the lower the overall survival rate of the patients (all p < 0.05). After the knockdown of RP11, HCC cells displayed inhibited proliferation, increased apoptosis rate, and G1/S arrest. Moreover, the expression of cleaved PARP1 and cleaved caspase-3 was increased. GO enrichment and KEGG pathway enrichment analysis showed some important pathways that might be related to the knockdown of RP11 in HCC cells. lncRNA RP11 is an HCC-promoting gene and a potential prognostic predictor of HCC.

Epigenetic dysregulated long non-coding RNAs in renal cell carcinoma based on multi-omics data and their influence on target drugs sensibility.

Epigenetic modifications play a crucial role in cancer development, and our study utilized public data to analyze which leads to the discovery of significant epigenetic abnormalities in lncRNAs, offering valuable insights into prognosis and treatment strategies for renal carcinoma. Public data were obtained from the Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) database. The analysis of the online public data was all completed in R software. We discovered a great number of epigenetic abnormalities of lncRNA in renal cancer, which is achieved by comparing the following modification and methylation of histone region changes on the promoter and enhancer of lncRNA: H3K27ac, H3K4me1, H3K4me3. As a result, 12 specific epigenetic disorders of lncRNA genes in renal cancer were identified. Finally, based on this lncRNA, we investigated the prognosis of renal cancer samples, among which 8 lncRNA can be seen as markers of prognosis in renal cancer, which had great prediction ability for ccRCC prognosis. Meanwhile, high risk score may pose response better to axitinib and nilotinib, but not sorafenib or sunitinib. Beyond, we observed an elevated level of risk score in immunotherapy non-responders. Further, biological enrichment and immuno-infiltration analysis was conducted to investigate the fundamental differences between patients categorized as high or low risk. Our research improves the understanding in the function of epigenetic dysregulated long non-coding RNAs in renal carcinoma.

Novel insights on oral squamous cell carcinoma management using long non-coding RNAs.

Oral squamous cell carcinoma (OSCC) is one of the most prevalent forms of head and neck squamous cell carcinomas (HNSCC) with a poor overall survival rate (about 50%), particularly in cases of metastasis. RNA-based cancer biomarkers are a relatively advanced concept, and non-coding RNAs currently have shown promising roles in the detection and treatment of various malignancies. This review underlines the function of long non-coding RNAs (lncRNAs) in the OSCC and its subsequent clinical implications. LncRNAs, a class of non-coding RNAs, are larger than 200 nucleotides and resemble mRNA in numerous ways. However, unlike mRNA, lncRNA regulates multiple druggable and non-druggable signaling molecules through simultaneous interaction with DNA, RNA, proteins, or microRNAs depending on concentration and localization in cells. Upregulation of oncogenic lncRNAs and down-regulation of tumor suppressor lncRNAs are evident in OSCC tissues and body fluids such as blood and saliva indicating their potential as valuable biomarkers. Targeted inhibition of candidate oncogenic lncRNAs or over-expression of tumor suppressor lncRNAs showed potential therapeutic roles in in-vivo animal models. The types of lncRNAs that are expressed differentially in OSCC tissue and bodily fluids have been systematically documented with specificity and sensitivity. This review thoroughly discusses the biological functions of such lncRNAs in OSCC cell survival, proliferation, invasion, migration, metastasis, angiogenesis, metabolism, epigenetic modification, tumor immune microenvironment, and drug resistance. Subsequently, we addressed the diagnostic and therapeutic importance of lncRNAs in OSCC pre-clinical and clinical systems, providing details on ongoing research and outlining potential future directions for advancements in this field. In essence, this review could be a valuable resource by offering comprehensive and current insights into lncRNAs in OSCC for researchers in fundamental and clinical domains.

LncRNA pol-lnc78 as a ceRNA regulates antibacterial responses via suppression of pol-miR-n199-3p-mediated SARM down-regulation in Paralichthys olivaceus.

Long non-coding RNAs (lncRNAs) function as key modulators in mammalian immunity, particularly due to their involvement in lncRNA-mediated competitive endogenous RNA (ceRNA) crosstalk. Despite their recognized significance in mammals, research on lncRNAs in lower vertebrates remains limited. In the present study, we characterized the first immune-related lncRNA (pol-lnc78) in the teleost Japanese flounder ( Paralichthys olivaceus). Results indicated that pol-lnc78 acted as a ceRNA for pol-miR-n199-3p to target the sterile alpha and armadillo motif-containing protein (SARM), the fifth discovered member of the Toll/interleukin 1 (IL-1) receptor (TIR) adaptor family. This ceRNA network regulated the antibacterial responses of flounder via the Toll-like receptor (TLR) signaling pathway. Specifically, SARM acted as a negative regulator and exacerbated bacterial infection by inhibiting the expression of inflammatory cytokines IL-1β and tumor necrosis factor-α (TNF-α). Pol-miR-n199-3p reduced SARM expression by specifically interacting with the 3' untranslated region (UTR), thereby promoting SARM-dependent inflammatory cytokine expression and protecting the host against bacterial dissemination. Furthermore, pol-lnc78 sponged pol-miR-n199-3p to ameliorate the inhibition of SARM expression. During infection, the negative regulators pol-lnc78 and SARM were significantly down-regulated, while pol-miR-n199-3p was significantly up-regulated, thus favoring host antibacterial defense. These findings provide novel insights into the mechanisms underlying fish immunity and open new horizons to better understand ceRNA crosstalk in lower vertebrates.

Integrative analysis of long noncoding RNAs dysregulation and synapse-associated ceRNA regulatory axes in autism

Autism spectrum disorder (ASD) is a complex disorder of neurodevelopment, the function of long noncoding RNA (lncRNA) in ASD remains essentially unknown. In the present study, gene networks were used to explore the ASD disease mechanisms integrating multiple data types (for example, RNA expression, whole-exome sequencing signals, weighted gene co-expression network analysis, and protein-protein interaction) and datasets (five human postmortem datasets). A total of 388 lncRNAs and five co-expression modules were found to be altered in ASD. The downregulated co-expression M4 module was significantly correlated with ASD, enriched with autism susceptibility genes and synaptic signaling. Integrating lncRNAs from the M4 module and microRNA (miRNA) dysregulation data from the literature identified competing endogenous RNA (ceRNA) network. We identified the downregulated mRNAs that interact with miRNAs by the miRTarBase, miRDB, and TargetScan databases. Our analysis reveals that MIR600HG was downregulated in multiple brain tissue datasets and was closely associated with 9 autism-susceptible miRNAs in the ceRNA network. MIR600HG and target mRNAs (EPHA4, MOAP1, MAP3K9, STXBP1, PRKCE, and SCAMP5) were downregulated in the peripheral blood by quantitative reverse transcription polymerase chain reaction analysis (false discovery rate <0.05). Subsequently, we assessed the role of lncRNA dysregulation in altered mRNA levels. Experimental verification showed that some synapse-associated mRNAs were downregulated after the MIR600HG knockdown. BrainSpan project showed that the expression patterns of MIR600HG (primate-specific lncRNA) and synapse-associated mRNA were similar in different human brain regions and at different stages of development. A combination of support vector machine and random forest machine learning algorithms retrieved the marker gene for ASD in the ceRNA network, and the area under the curve of the diagnostic nomogram was 0.851. In conclusion, dysregulation of MIR600HG, a novel specific lncRNA associated with ASD, is responsible for the ASD-associated miRNA-mRNA axes, thereby potentially regulating synaptogenesis.

A Notch signaling-related lncRNA signature for predicting prognosis and therapeutic response in clear cell renal cell carcinoma

Increasing evidence has confirmed the vital role of Notch signaling in the tumorigenesis of clear cell renal cell carcinoma (ccRCC). The underlying function of long non-coding RNA (lncRNA) related to Notch signaling in ccRCC remains unclear. In present study, the prognostic value and therapeutic strategy of Notch signaling-related lncRNA are comprehensively explored in ccRCC. In total, we acquired 1422 NSRlncRNAs, of which 41 lncRNAs were identified the key NSRlncRNAs associated with the occurrence of ccRCC. The prognostic signature containing five NSRlncRNAs (AC092611.2, NNT-AS1, AGAP2-AS1, AC147651.3, and AC007406.3) was established and validated, and the ccRCC patients were clustered into the high- and low-risk groups. The overall survival of patients in the low-risk group were much more favorable than those in the high-risk group. Multivariate Cox regression analysis indicated that the risk score was an independent prognostic biomarker. Based on the risk score and clinical variables, a nomogram for predicting prognosis of ccRCC patients was constructed, and the calibration curves and DCA curves showed the superior predictive ability of nomogram. The risk score was correlated with immune cell infiltration, targeted therapy or chemotherapy sensitivity, and multiple oncogenic pathways. Additionally, consensus clustering analysis stratified the ccRCC patients into four clusters with obvious different outcomes, immune microenvironments, and expression of immune checkpoints. The constructed NSRlncRNA-based signature might serve as a potential biomarker for predicting prognosis and response to immunotherapy or targeted therapy in patients with ccRCC.

LINC02561 promotes metastasis in HCC via HIF1-α/NDRG1/UPF1 axis

In the entire world, hepatocellular carcinoma (HCC) is one of the most frequent cancers that lead to death. Experiments on the function of long non-coding RNAs in the emergence of malignancies, including HCC, are ongoing. As a crucial RNA monitoring mechanism in eucaryotic cells, nonsense-mediated mRNA decay (NMD) can recognize and destroy mRNAs, which has an premature termination codons (PTC) in the open reading frame to prevent harmful buildup of truncated protein products in the cells. Nonsense transcript regulator 1 (Up-frameshift suppressor 1, UPF1), as a highly conserved RNA helicase and ATPase, plays a key role in NMD. Our laboratory screened out the highly expressed lncRNA LINC02561 in HCC from the TCGA database. Further research found that LINC02561 enhanced the invasion and transition abilities of liver cancer cells by regulating the protein N-Myc downstream regulated 1 (NDRG1). Hypoxia inducible factor-1 (HIF-1α) can bonded to LINC02561 promoters under hypoxic conditions, thereby promoting the upregulation of LINC02561 expression in liver cancer cells. LINC02561 competes with NDRG1 mRNA to bind UPF1, thereby preventing the degradation of NDRG1 mRNA to facilitate NDRG1 protein level. Taken together, the HIF1α-LINC02561-UPF1-NDRG1 regulatory axis could be an entirely novel target of liver cancer-related treatment.

SINE-Associated LncRNA SAWPA Regulates Porcine Zygotic Genome Activation.

In mice, retrotransposon-associated long noncoding RNAs (lncRNA) play important regulatory roles in pre-implantation development; however, it is largely unknown whether they function in the pre-implantation development in pigs. The current study aims to screen for retrotransposon-associated lncRNA in porcine early embryos and identifies a porcine 8-cell embryo-specific SINE-associated nuclear long noncoding RNA named SAWPA. SAWPA is essential for porcine embryonic development as depletion of SAWPA results in a developmental arrest at the 8-cell stage, accompanied by the inhibition of the JNK-MAPK signaling pathway. Mechanistically, SAWPA works in trans as a transcription factor for JNK through the formation of an RNA-protein complex with HNRNPA1 and MED8 binding the SINE elements upstream of JNK. Therefore, as the first functional SINE-associated long noncoding RNAs in pigs, SAWPA provides novel insights for the mechanism research on retrotransposons in mammalian pre-implantation development.

EVLncRNAs 3.0: an updated comprehensive database for manually curated functional long non-coding RNAs validated by low-throughput experiments.

Long noncoding RNAs (lncRNAs) have emerged as crucial regulators across diverse biological processes and diseases. While high-throughput sequencing has enabled lncRNA discovery, functional characterization remains limited. The EVLncRNAs database is the first and exclusive repository for all experimentally validated functional lncRNAs from various species. After previous releases in 2018 and 2021, this update marks a major expansion through exhaustive manual curation of nearly 25000 publications from 15May 2020, to 15May 2023. It incorporates substantial growth across all categories: a 154% increase in functional lncRNAs, 160% in associated diseases, 186% in lncRNA-disease associations, 235% in interactions, 138% in structures, 234% in circular RNAs, 235% in resistant lncRNAsand 4724% in exosomal lncRNAs. More importantly, it incorporated additional information include functional classifications, detailed interaction pathways, homologous lncRNAs, lncRNA locations, COVID-19, phase-separation and organoid-related lncRNAs. The web interface was substantially improved for browsing, visualization, and searching. ChatGPT was tested for information extraction and functional overview with its limitation noted. EVLncRNAs 3.0 represents the most extensive curated resource of experimentally validated functional lncRNAs and will serve as an indispensable platform for unravelling emerging lncRNA functions. The updated database is freely available at https://www.sdklab-biophysics-dzu.net/EVLncRNAs3/.

54 Large-Scale Crispr Functional Characterization of Genomic Elements in Rainbow Trout (Oncorhynchus mykiss)

Abstract The wealth of genetic information that is now available for many agricultural animal species has opened vast potential to apply this new knowledge to improve agricultural production and sustainability. The field, however, is now faced with the daunting task of trying to understand what is arguably the most complex coded system known to mankind. In biomedical model systems, extensive efforts over decades have used single candidate gene approaches to uncover the function of many protein-coding genes and non-coding RNAs, but how this information translates to agricultural animals and their production traits is often unknown. Not only is repeating this vast effort for every agricultural species not practical, the current pace of genomic discovery is woefully inadequate for investigating animal genomes and therefore a radically new approach is needed. Using rainbow trout (RBT, Oncorhynchus mykiss) as a novel agricultural animal experimental system we have initiated a large-scale functional genomics screen that aims to characterize the function of over 1,000 genomic elements in a large animal model. The initial screen will focus on understanding how different genomic elements regulate growth and environmental resilience in these fish by combining multiplex CRISPR genome editing technology and phenotypic screening approaches to identify novel allele combinations from families of edited fish. The research is a paradigm shift in our approach to characterizing gene function, moving away from candidate-based approaches to a more genomics view of gene function. This work will shed light on the complex genetic mechanisms underlying two important production traits in fish while helping to advance our understanding of large animal functional genomics.

Role of Non-coding RNA in the Pathogenesis of Intestinal Ischemia- Reperfusion Injury.

Intestinal ischemia-reperfusion injury is a relatively common clinical condition that seriously threatens the prognosis of patients; however, the exact mechanism of intestinal ischemia-reperfusion injury has not been clarified. Recent studies have found that noncoding RNAs, including but not limited to lncRNA, circRNA, and miRNA, play an important role in the pathogenesis of intestinal ischemia-reperfusion. The findings cited in this paper reveal the expression, function, and mechanism of noncoding RNAs during intestinal ischemia-reperfusion. The mechanistic roles of noncoding RNAs in the occurrence and development of intestinal ischemia-reperfusion are discussed, including cell proliferation, autophagy, oxidative stress, apoptosis, oxidative stress, iron death, and many other aspects. However, many unknown mechanisms of association between noncoding RNAs and intestinal ischemia-reperfusion remain to be investigated.

Long Non-Coding RNA Dancr Affects Myocardial Fibrosis in Atrial Fibrillation Mice via the MicroRNA-146b-5p/Smad5 Axis.

Atrial fibrillation (AF) is the most frequent arrhythmia, and myocardial fibrosis (MF) has a close association with atrial remodeling and leads to AF. This study aimed to explore the function of the long non-coding RNA (lncRNA) differentiation antagonizing non-protein coding RNA (Dancr)/microRNA (miR)-146b-5p/Smad5 axis on MF in AF mice. AF mouse models were established. Overexpression Dancr lentivirus was injected into AF mice to increase Dancr expression in myocardial tissues. LncRNA Dancr, miR-146b-5p, and Smad5 expression levels and inflammatory factors (IL-18 and TNF-α) in the myocardial tissues were measured. MF was measured and the expression levels of MF-related genes (COL1A1, α-SMA, and FN1) were detected. In addition, in vitro HL-1 cell rapid pacing models were constructed, and after lncRNA Dancr and miR-146b-5p-related construct transfection, cell viability and cell apoptosis were determined. LncRNA Dancr up-regulation ameliorated MF in the AF mice, reduced IL-18 and TNF-α expression levels in myocardial tissues, and decreased COL1A1, α-SMA, and FN1 expression levels. The in vitro HL-1 cell rapid pacing models suggested that miR-146b-5p overexpression reversed the inhibitory effects of lncRNA Dancr overexpression on MF in HL-1 cells, and Smad5 interference reversed the ameliorative effects of miR-146b-5p interference on MF in HL-1 cells. LncRNA Dancr can sponge miR-146b-5p to promote Smad5 expression, thereby delaying MF in AF mice.

Digging out the biology properties of tRNA-derived small RNA from black hole.

An unique subclass of functional non-coding RNAs generated by transfer RNA (tRNA) under stress circumstances is known as tRNA-derived small RNA (tsRNA). tsRNAs can be divided into tRNA halves and tRNA-derived fragments (tRFs) based on the different cleavage sites. Like microRNAs, tsRNAs can attach to Argonaute (AGO) proteins to target downstream mRNA in a base pairing manner, which plays a role in rRNA processing, gene silencing, protein expression and viral infection. Notably, tsRNAs can also directly bind to protein and exhibit functions in transcription, protein modification, gene expression, protein stabilization, and signaling pathways. tsRNAs can control the expression of tumor suppressor genes and participate in the initiation of cancer. It can also mediate the progression of diseases by regulating cell viability, migration ability, inflammatory factor content and autophagy ability. Precision medicine targeting tsRNAs and drug therapy of plant-derived tsRNAs are expected to be used in clinical practice. In addition, liquid biopsy technology based on tsRNAs indicates a new direction for the non-invasive diagnosis of diseases.

Deciphering the Functional Long Non-Coding RNAs Derived from MicroRNA Loci.

Albeit the majority of eukaryotic genomes can be pervasively transcribed to a diverse population of lncRNAs and various subtypes of lncRNA are discovered. However, the genome-wide study of miRNA-derived lncRNAs is still lacking. Here, it is reported that over 800 miRNA gene-originated lncRNAs (molncRNAs) are generated from miRNA loci. One of them, molnc-301b from miR-301b and miR-130b, functions as an "RNA decoy" to facilitate dissociation of the chromatin remodeling protein SMARCA5 from chromatin and thereby sequester transcription and mRNA translation. Specifically, molnc-301b attenuates erythropoiesis by mitigating the transcription of erythropoietic and translation-associated genes, such as GATA1 and FOS. In addition, a useful and powerful CRISPR screen platform to characterize the biological functions of molncRNAs at large-scale and single-cell levels is established and 29 functional molncRNAs in hematopoietic cells are identified. Collectively, the focus is on miRNA-derived lncRNAs, deciphering their landscape during normal hematopoiesis, and comprehensively evaluating their potential roles.