Post-transcriptional Processes Research Articles

Is bRaQCing bad? New roles for ribosome associated quality control factors in stress granule regulation.

Maintenance of proteostasis is of utmost importance to cellular viability and relies on the coordination of many post-transcriptional processes to respond to stressful stimuli. Stress granules (SGs) are RNA-protein condensates that form after translation initiation is inhibited, such as during the integrated stress response (ISR), and may facilitate cellular adaptation to stress. The ribosome-associated quality control (RQC) pathway is a critical translation monitoring system that recognizes aberrant mRNAs encoding potentially toxic nascent peptides to target them for degradation. Both SG regulation and the RQC pathway are directly associated with translation regulation, thus it is of no surprise recent developments have demonstrated a connection between them. VCP's function in the stress activated RQC pathway, ribosome collisions activating the ISR, and the regulation of the 40S ribosomal subunit by canonical SG proteins during the RQC all connect SGs to the RQC pathway. Because mutations in genes that are involved in both SG and RQC regulation are associated with degenerative and neurological diseases, understanding the coordination and interregulation of SGs and RQC may shed light on disease mechanisms. This minireview will highlight recent advances in understanding how SGs and the RQC pathway interact in health and disease contexts.

The mechanical regulation of RNA binding protein hnRNPC in the failing heart.

Cardiac pathologies are characterized by intense remodeling of the extracellular matrix (ECM) that eventually leads to heart failure. Cardiomyocytes respond to the ensuing biomechanical stress by reexpressing fetal contractile proteins via transcriptional and posttranscriptional processes, such as alternative splicing (AS). Here, we demonstrate that the heterogeneous nuclear ribonucleoprotein C (hnRNPC) is up-regulated and relocates to the sarcomeric Z-disc upon ECM pathological remodeling. We show that this is an active site of localized translation, where the ribonucleoprotein associates with the translation machinery. Alterations in hnRNPC expression, phosphorylation, and localization can be mechanically determined and affect the AS of mRNAs involved in mechanotransduction and cardiovascular diseases, including Hippo pathway effector Yes-associated protein 1.We propose that cardiac ECM remodeling serves as a switch in RNA metabolism by affecting an associated regulatory protein of the spliceosome apparatus. These findings offer new insights on the mechanism of mRNA homeostatic mechanoregulation in pathological conditions.

Tsukushi proteoglycan maintains RNA splicing and developmental signaling network in GFAP-expressing subventricular zone neural stem/progenitor cells.

Tsukushi (TSK) proteoglycan dysfunction leads to hydrocephalus, a condition defined by excessive fluid collection in the ventricles and lateral ventricular enlargement. TSK injections into the LV at birth are effective at rescuing the lateral ventricle (LV). TSK regulates the activation of the Wnt signaling to facilitate the proper expansion of the LV and maintain the fate of the neural stem cell lineage. However, the molecular mechanism by which TSK acts on neural stem/progenitor cells (NSCs) during LV development is unknown. We demonstrated that TSK is crucial for the splicing and development-associated gene regulation of GFAP-expressing subventricular zone (SVZ) NSCs. We isolated GFAP-expressing NSCs from the SVZ of wild-type (GFAPGFP/+/TSK+/+) and TSK knock-out (GFAPGFP/+/TSK-/-) mice on postnatal day 3 and compared their transcriptome and splicing profiles. TSK deficiency in NSCs resulted in genome-wide missplicing (alteration in exon usage) and transcriptional dysregulation affecting the post-transcriptional regulatory processes (including splicing, cell cycle, and circadian rhythm) and developmental signaling networks specific to the cell (including Wnt, Sonic Hedgehog, and mTOR signaling). Furthermore, TSK deficiency prominently affected the splicing of genes encoding RNA and DNA binding proteins in the nervous SVZ and non-nervous muscle tissues. These results suggested that TSK is involved in the maintenance of correct splicing and gene regulation in GFAP-expressing NSCs, thereby protecting cell fate and LV development. Hence, our study provides a critical insight on hydrocephalus development.

473 DUSP4-DUSP6 axis contributes to sustained ERK activity and high proliferation of the melanoma cells

A subset of dual-specificity phosphatases (DUSPs) act as major negative regulators of mitogen-activated protein kinases (MAPKs), and their possible involvement in tumorigenesis has been suggested. Among them, DUSP4 preferentially dephosphorylates ERK1/2 and Jnk over p38. In the present study, we aimed to identify the possible role of DUSP4 in melanomagenesis. Examination of publicly available large-scale data on cancer cell-lines revealed a remarkably high DUSP4 expression and dependency of most melanoma cell lines compared with other tumor-derived cell lines. No such high gene dependency specific to melanoma cells was evident for the other 24 DUSPs encoded in the human genome. Using two melanoma cell lines SK-MEL-28 and A375 as representatives, we confirmed that DUSP4 depletion impaired cell growth without notably inducing apoptosis for up to several days. Immunoblotting and kinase translocation reporter assay showed that the depletion simultaneously induced a decrease, not an increase, in ERK1/2 phosphorylation and an increase in DUSP6 protein level and that it barely affected Jnk phosphorylation. This observation indicates that neither ERK nor Jnk was a direct target of DUSP4 in our experimental setting. Quantitation of DUSP6 mRNA suggested that change in DUSP6 protein level mainly occurred through a post-transcriptional process, although it is not clear whether this took place by an increase in translation rate or inhibition of degradation kinetics. CRISPR/CAS9-mediated knock-out of DUSP6 mostly eliminated a decrease in the ERK phosphorylation and growth retardation following DUSP4 depletion suggesting the existence of the DUSP4-DUSP6-ERK serial regulation pathway. Our data support a model that DUSP4 plays a role in maintaining high ERK1/2 activity by negatively regulating DUSP6, thus contributing to the survival and growth of melanoma cells.

Molecular responses to acute exercise and their relevance for adaptations in skeletal muscle to exercise training.

Repeated, episodic bouts of skeletal muscle contraction undertaken frequently as structured exercise training are a potent stimulus for physiological adaptation in many organs. Specifically, in skeletal muscle, remarkable plasticity is demonstrated by the remodeling of muscle structure and function in terms of muscular size, force, endurance, and contractile velocity as a result of the functional demands induced by various types of exercise training. This plasticity, and the mechanistic basis for adaptations to skeletal muscle in response to exercise training, are underpinned by activation and/or repression of molecular pathways and processes in response to each individual acute exercise session. These pathways include the transduction of signals arising from neuronal, mechanical, metabolic, and hormonal stimuli through complex signal transduction networks, which are linked to a myriad of effector proteins involved in the regulation of pre- and posttranscriptional processes, and protein translation and degradation processes. This review therefore describes acute exercise-induced signal transduction and the molecular responses to acute exercise in skeletal muscle including emerging concepts such as epigenetic pre- and posttranscriptional regulation and the regulation of protein translation and degradation. A critical appraisal of methodological approaches and the current state of knowledge informs a series of recommendations offered as future directions in the field.

Cucumber STACHYOSE SYNTHASE is regulated by its cis-antisense RNA asCsSTS to balance source-sink carbon partitioning.

Photosynthate partitioning between source and sink is a key determinant of crop yield. In contrast to sucrose-transporting plants, cucumber (Cucumis sativus) plants mainly transport stachyose and stachyose synthase (CsSTS) synthesizes stachyose in the vasculature for loading. Therefore, CsSTS is considered a key regulator of carbon partitioning. We found that CsSTS expression and CsSTS enzyme activity were upregulated in the vasculature and downregulated in mesophyll tissues at fruiting. In situ hybridization and tissue enrichment experiments revealed that a cis-natural antisense noncoding transcript of CsSTS, named asCsSTS, is mainly expressed in mesophyll tissues. In vitro overexpression (OE), RNA interference (RNAi), and dual luciferase reporter experiments indicated that CsSTSs are negatively regulated by asCsSTS. Fluorescence in situ hybridization revealed that asCsSTS transcript localized in leaf cytoplasm, indicating that the regulation of CsSTS by asCsSTS is a posttranscriptional process. Further investigation revealed that this regulation occurred by reducing CsSTS transcript stability through a DICER-like protein-mediated pathway. Chemically induced OE and RNAi of asCsSTS led to promotion or inhibition, respectively, of assimilate export from leaves and altered fruit growth rates. Our results suggest that the regulation of CsSTSs between the mesophyll and vasculature reduces sugar storage in mesophyll tissue and promotes assimilate export from the leaf when the plant carries fruit.

Exploring the RNA Editing Events and Their Potential Regulatory Roles in Tea Plant (Camellia sinensis L.).

RNA editing is a post-transcriptional modification process that alters the RNA sequence relative to the genomic blueprint. In plant organelles (namely, mitochondria and chloroplasts), the most common type is C-to-U, and the absence of C-to-U RNA editing results in abnormal plant development, such as etiolation and albino leaves, aborted embryonic development and retarded seedling growth. Here, through PREP, RES-Scanner, PCR and RT-PCR analyses, 38 and 139 RNA editing sites were identified from the chloroplast and mitochondrial genomes of Camellia sinensis, respectively. Analysis of the base preference around the RNA editing sites showed that in the -1 position of the edited C had more frequent occurrences of T whereas rare occurrences of G. Three conserved motifs were identified at 25 bases upstream of the RNA editing site. Structural analyses indicated that the RNA secondary structure of 32 genes, protein secondary structure of 37 genes and the three-dimensional structure of 5 proteins were altered due to RNA editing. The editing level analysis of matK and ndhD in six tea cultivars indicated that matK-701 might be involved in the color change of tea leaves. Furthermore, 218 PLS-CsPPR proteins were predicted to interact with the identified RNA editing sites. In conclusion, this study provides comprehensive insight into RNA editing events, which will facilitate further study of the RNA editing phenomenon of the tea plant.

YTHDF3 promotes melanoma metastasis by reading N6‐methyladenosine

YTHDF3 promotes melanoma metastasis by reading N⁶‐methyladenosine

IL-6/Stat3 suppresses osteogenic differentiation in ossification of the posterior longitudinal ligament via miR-135b-mediated BMPER reduction.

Interleukin-6 (IL-6) has been reported to induce osteogenic differentiation of mesenchymal stem cells for increasing bone regeneration, while the role of IL-6 in osteogenic differentiation during ossification of the posterior longitudinal ligament (OPLL) remains to be determined. The current study aims to explore the downstream mechanism of IL-6 in cyclic tensile strain (CTS)-stimulated OPLL, which involves bioinformatically identified microRNA-135b (miR-135b). Initially, we clinically collected posterior longitudinal ligament (PLL) and ossified PLL tissues, from which ossified PLL cells were isolated, respectively. The obtained data revealed a greater osteogenic property of ossified PLL than non-ossified PLL cells. The effect of regulatory axis comprising IL-6, Stat3, miR-135b, and BMPER on osteogenic differentiation of CTS-stimulated ossified PLL cells was examined with gain- and loss-of-function experiments. BMPER was confirmed as a target gene to miR-135b. Knockdown of BMPER or overexpression of miR-135b inhibited the osteogenic differentiation of CTS-induced ossification in PLL cells. Besides, IL-6 promoted the post-transcriptional process to mature miR-135b via Stat3 phosphorylation. In conclusion, IL-6 inhibited CTS-induced osteogenic differentiation by inducing miR-135b-mediated inhibition of BMPER through Stat3 activation.

Decrease of RNA editing in the failing heart leads to induction of circRNAs

Abstract Background and purpose Adenosine-to-Inosine (A-to-I) RNA editing is a post-transcriptional modification process that affects the secondary structure of RNAs. Changes in RNA editing have been associated with human diseases. We therefore aimed to analyze editing in the healthy and failing human heart. Methods and results Transcriptome sequencing of human heart samples of heart failure (HF) patients (n=20) and controls (n=10) revealed A-to-I editing as the major type of editing (>80%). In HF patients, RNA editing was reduced, which was primarily attributable to Alu elements in introns of protein-coding genes. We identified 166 upregulated circRNAs in HF, with the majority showing reduced RNA editing in their parental host gene (88.3%). CircRNA expression did not correlate with their corresponding host gene (R=0.07, P<0.05), suggesting that an alternative splicing mechanism gives rise to the elevated circRNA levels in HF. The RNA editing enzyme ADAR2, which binds to RNA regions that are edited from adenosine to inosine, was decreased in failing human hearts (−68.2%). In vitro, reduction of ADAR2 increased circRNA levels suggesting a causal effect of reduced ADAR2 levels on increased circRNAs in the failing human heart. To gain mechanistic insight, we examined the formation of circRNAs on one exemplary candidate. AKAP13 was among the top edited mRNAs in the human heart and gave rise to a circular transcript, which was elevated in HF. ADAR2 reduced the formation of double-stranded structures in AKAP13 pre-mRNA, thereby reducing the stability of Alu elements and the circularization of the resulting circRNA. Overexpression of circAKAP13 impaired the sarcomere regularity of human induced pluripotent stem cell-derived cardiomyocytes (−31.0%). Conclusion Our study shows that ADAR2 mediates A-to-I RNA editing in the human heart. We describe an alternative splicing mechanism of circRNAs in the human heart. In the healthy human heart, A-to-I RNA editing represses the formation of dsRNA structures of Alu elements thereby favoring linear mRNA splicing. Our results contribute to a better mechanistic understanding into the human-specific regulation of circRNA formation and are relevant to diseases with reduced RNA editing and increased circRNA levels. Funding Acknowledgement Type of funding sources: None.

Advances in Data Repositories for ncRNA-Protein Interaction Predictions Based on Machine Learning: A Mini-Review

Background: This study aims at exploring the advances in data repositories for predicting interactions between non-coding RNAs (ncRNAs) and corresponding proteins. NcRNAs are a class of ribonucleic acid that lacks the potential for protein translation. A series of studies indicated that ncRNAs play critical roles in epigenetic regulations, chromatin remodeling, transcription process, and post-transcriptional processing. Since ncRNAs function with associated proteins during complex biological procedures, it is important to identify ncRNA-protein interactions, which will provide guidance for exploring the internal molecular mechanisms. Recently, a variety of machine learning methods have emerged, with the lower cost and time-saving advantages compared to experimental methods. In machine learning, the performance of classification models is often affected by the quality of input samples and their features. Aim: Thus, the study intends to introduce the related data sources used in predicting ncRNAprotein interactions (ncRPIs) based on machine learning. Methods: We searched related literature from different sources, including PubMed, Web of Science, and Scopus, using the search terms “machine learning”, “repository”, “non-coding RNA”, and “protein”. In this work, we described the databases applied to the dataset construction and feature representation in the ncRPIs prediction task. Results: This study reviews the application of the benchmark dataset construction and conventional feature representation during ncRPI prediction processes. Furthermore, the source, main functions, and development status of each database are also discussed in this work. Conclusion: With the development of high-throughput technologies for generating ncRPIs and constructing related databases, machine learning would become a necessary research means, enriching the prediction methods of ncRPIs. Due to an increase in improved databases, the resources of molecular structures, functions, and genetic information for data mining have increased, enhancing the credibility of ncRPI prediction based on machine learning. We believe that the databases will be more widely used in disease research, drug development, and many other fields.

VP.02 Comprehensive characterization of early-onset skeletal muscle disease gene exon usage and splicing patterns across different developmental ages

Alternative splicing is a normal post-transcriptional regulation process that facilitates the generation of multiple different protein isoforms from the one gene. This results in the production of a family protein isoforms uniquely suited to the needs of each tissue subtype and developmental stage. There is an increasing body of evidence to suggest that disease-causing variants that impact exons that are not "used" by highly abundant isoform transcripts might have less clinical impact. However, it is also increasingly clear that some exons encode regions of isoforms that perform important functional roles during critical developmental windows. They might not be highly used by all isoforms, but their inclusion within some transcripts is hugely important. Our overall understanding of normal skeletal and cardiac muscle exon usage and splicing patterns is extremely limited. This is adversely impacting our ability to understand how exon usage impacts clinical variability. In addition, due to recent bioinformatic advances, our ability to identify variants that might be adversely impacting normal exons usage and splicing patterns (potential splice-impacting variants) is rapidly improving. However, our limited understanding of "what is normal" is hampering our ability functionally validate these variants. In this study, we characterized the normal exon usage and splicing patterns of a range of important congenital and early onset skeletal muscle disease genes in different healthy skeletal and cardiac muscle subtypes across different developmental ages (fetal to adult). For some genes, exon usage and splicing patterns within specific regions of the transcript varied greatly across different tissues and/or developmental ages. Our study significantly expands our understanding of healthy striated muscle isoform biology and the relationship between alternative splicing patterns and skeletal muscle disease.

Comprehensive analysis of transcriptome and metabolome analysis reveal new targets of Glaesserella parasuis glucose-specific enzyme IIBC (PtsG)

The ptsG (hpIIBCGlc) gene, belonging to the glucose-specific phosphotransferase system, encodes the bacterial glucose-specific enzyme IIBC. In this study, the effects of a deletion of the ptsG gene were investigated by metabolome and transcriptome analyses. At the transcriptional level, we identified 970 differentially expressed genes between ΔptsG and sc1401 (Padj<0.05) and 2072 co-expressed genes. Among these genes, those involved in methane metabolism, amino sugar and nucleotide sugar metabolism, starch and sucrose metabolism, pyruvate metabolism, phosphotransferase system (PTS), biotin metabolism, Two-component system and Terpenoid backbone biosynthesis showed significant changes in the ΔptsG mutant strain. Metabolome analysis revealed that a total of 310 metabolites were identified, including 20 different metabolites (p < 0.05). Among them, 15 metabolites were upregulated and 5 were downregulated in ΔptsG mutant strain. Statistical analysis revealed there were 115 individual metabolites having correlation, of which 89 were positive and 26 negative. These metabolites include amino acids, phosphates, amines, esters, nucleotides, benzoic acid and adenosine, among which amino acids and phosphate metabolites dominate. However, not all of these changes were attributable to changes in mRNA levels and must also be caused by post-transcriptional regulatory processes. The knowledge gained from this lays the foundation for further study on the role of ptsG in the pathogenic process of Glaesserella parasuis (G.parasuis).

Effects of collagen type ⅩⅦ α1 on epidermal stem cells in aging skin and the microRNA intervention mechanism

Effects of collagen type ⅩⅦ α1 on epidermal stem cells in aging skin and the microRNA intervention mechanism

Genome-wide identification of RNA editing sites in chloroplast transcripts and multiple organellar RNA editing factors in tea plant (Camellia sinensis L.): Insights into the albinism mechanism of tea leaves

RNA editing is a post-transcriptional modification process, the chloroplast genes of which are involved in the process of chloroplast development in plant. However, the RNA editing sites of chloroplast genes remains unknown. In this study, we identified 39 RNA editing sites in 18 chloroplast genes from chloroplast genome of C. sinensis. Furthermore, the feature, structures and specificity of RNA editing sites were systematic analyzed. The differential editing efficiency were examined at 11 RNA editing sites among C. sinensis var. sinensis ‘Huabai 1′, ‘Baiye 1′ and ‘Longjing 43′. Meanwhile, we identified 10 C. sinensis MORFs from five subgroups and performed comparative analyses of chromosome locations, duplication model and expression profiles. Expression analysis showed that the expression level of CsMORF9.2 was down-regulated significantly in ‘Huabai 1′ albino tea cultivar. This study provides a foundation for further reveal in the role of chloroplast RNA editing in albinism process of tea leaves.

RNA-binding protein signaling in adult neurogenesis.

The process of neurogenesis in the brain, including cell proliferation, differentiation, survival, and maturation, results in the formation of new functional neurons. During embryonic development, neurogenesis is crucial to produce neurons to establish the nervous system, but the process persists in certain brain regions during adulthood. In adult neurogenesis, the production of new neurons in the hippocampus is accomplished via the division of neural stem cells. Neurogenesis is regulated by multiple factors, including gene expression at a temporal scale and post-transcriptional modifications. RNA-binding Proteins (RBPs) are known as proteins that bind to either double- or single-stranded RNA in cells and form ribonucleoprotein complexes. The involvement of RBPs in neurogenesis is crucial for modulating gene expression changes and posttranscriptional processes. Since neurogenesis affects learning and memory, RBPs are closely associated with cognitive functions and emotions. However, the pathways of each RBP in adult neurogenesis remain elusive and not clear. In this review, we specifically summarize the involvement of several RBPs in adult neurogenesis, including CPEB3, FXR2, FMRP, HuR, HuD, Lin28, Msi1, Sam68, Stau1, Smaug2, and SOX2. To understand the role of these RBPs in neurogenesis, including cell proliferation, differentiation, survival, and maturation as well as posttranscriptional gene expression, we discussed the protein family, structure, expression, functional domain, and region of action. Therefore, this narrative review aims to provide a comprehensive overview of the RBPs, their function, and their role in the process of adult neurogenesis as well as to identify possible research directions on RBPs and neurogenesis.

Three tRNA nuclear exporters in S. cerevisiae: parallel pathways, preferences, and precision.

tRNAs that are transcribed in the nucleus are exported to the cytoplasm to perform their iterative essential function in translation. However, the complex set of tRNA post-transcriptional processing and subcellular trafficking steps are not completely understood. In particular, proteins involved in tRNA nuclear export remain unknown since the canonical tRNA nuclear exportin, Los1/Exportin-t, is unessential in all tested organisms. We previously reported that budding yeast Mex67-Mtr2, a mRNA nuclear exporter, co-functions with Los1 in tRNA nuclear export. Here we employed in vivo co-purification of tRNAs with endogenously expressed nuclear exporters to document that Crm1 also is a bona fide tRNA nuclear exporter. We document that Los1, Mex67-Mtr2 and Crm1 possess individual tRNA preferences for forming nuclear export complexes with members of the 10 families of intron-containing pre-tRNAs. Remarkably, Mex67-Mtr2, but not Los1 or Crm1, is error-prone, delivering tRNAs to the cytoplasm prior to 5′ leader removal. tRNA retrograde nuclear import functions to monitor the aberrant leader-containing spliced tRNAs, returning them to the nucleus where they are degraded by 3′ to 5′ exonucleases. Overall, our work identifies a new tRNA nuclear exporter, uncovers exporter preferences for specific tRNA families, and documents contribution of tRNA nuclear import to tRNA quality control.

A-to-I nonsynonymous RNA editing was significantly enriched in the ubiquitination site and correlated with clinical features and immune response

RNA editing is a post-transcriptional process that alters RNA sequence in a site-specific manner. A-to-I editing is the most abundant as well as the most well-studied type of RNA editing. About 0.5% of A-to-I editing sites were located in the coding regions. Despite of thousands of identified A-to-I nonsynonymous editing sites, the function of nonsynonymous editing was poorly studied. Here, we found that the nonsynonymous editing was significantly enriched in the ubiquitination site, compared to the synonymous editing. This enrichment was also in a modification type dependent manner, since it was not significantly enriched in other modification types. This observation was consistent with previous study that the codons for lysine (AAG and AAA) were enriched in the preferred deamination site for RNA editing. The peptides from proteomic data in CPTAC supported that mRNAs harboring edited ubiquitination sites can be translated into protein in cells. We identified the editing sites on ubiquitination site were significantly differential edited between tumor and para-tumor samples as well as among different subtypes in TCGA datasets and also correlated with clinical outcome, especially for the nonsynonymous editing sites on GSTM5, WDR1, SSR4 and PSMC4. Finally, the enrichment analysis revealed that the function of these above genes was specifically enriched in the immune response pathway. Our study shed a light on understanding the functions of nonsynonymous editing in tumorigenesis and provided nonsynonymous editing targets for potential cancer diagnosis and therapy.

Mobilisation of HLA-F on the surface of bronchial epithelial cells and platelets in asthmatic patients.

Uncontrolled inflammation of the airways in chronic obstructive lung diseases leads to exacerbation, accelerated lung dysfunction and respiratory insufficiency. Among these diseases, asthma affects 358million people worldwide. Human bronchial epithelium cells (HBEC) express both anti-inflammatory and activating molecules, and their deregulated expression contribute to immune cell recruitment and activation, especially platelets (PLT) particularly involved in lung tissue inflammation in asthma context. Previous results supported that HLA-G dysregulation in lung tissue is associated with immune cell activation. We investigated here HLA-F expression, reported to be mobilised on immune cell surface upon activation and displaying its highest affinity for the KIR3DS1-activating NK receptor. We explored HLA-F transcriptional expression in HBEC; HLA-F total expression in PBMC and HBEC collected from healthy individuals at rest and upon chemical activation and HLA-F membrane expression in PBMC, HBEC and PLT collected from healthy individuals at rest and upon chemical activation. We compared HLA-F transcriptional expression in HBEC from healthy individuals and asthmatic patients and its surface expression in HBEC and PLT from healthy individuals and asthmatic patients. Our results support that HLA-F is expressed by HBEC and PLT under healthy physiological conditions and is retained in cytoplasm, barely expressed on the surface, as previously reported in immune cells. In both cell types, HLA-F reaches the surface in the inflammatory asthma context whereas no effect is observed at the transcriptional level. Our study suggests that HLA-F surface expression is a ubiquitous post-transcriptional process in activated cells. It may be of therapeutic interest in controlling lung inflammation.

The Role of RNA-Binding Proteins in Hematological Malignancies.

Hematological malignancies comprise a plethora of different neoplasms, such as leukemia, lymphoma, and myeloma, plus a myriad of dysplasia, such as myelodysplastic syndromes or anemias. Despite all the advances in patient care and the development of new therapies, some of these malignancies remain incurable, mainly due to resistance and refractoriness to treatment. Therefore, there is an unmet clinical need to identify new biomarkers and potential therapeutic targets that play a role in treatment resistance and contribute to the poor outcomes of these tumors. RNA-binding proteins (RBPs) are a diverse class of proteins that interact with transcripts and noncoding RNAs and are involved in every step of the post-transcriptional processing of transcripts. Dysregulation of RBPs has been associated with the development of hematological malignancies, making them potential valuable biomarkers and potential therapeutic targets. Although a number of dysregulated RBPs have been identified in hematological malignancies, there is a critical need to understand the biology underlying their contribution to pathology, such as the spatiotemporal context and molecular mechanisms involved. In this review, we emphasize the importance of deciphering the regulatory mechanisms of RBPs to pinpoint novel therapeutic targets that could drive or contribute to hematological malignancy biology.