scholarly journals Fixed differences in the 3′UTR of buffalo PRNP gene provide binding sites for miRNAs post-transcriptional regulation

Oncotarget ◽  
2017 ◽  
Vol 8 (28) ◽  
pp. 46006-46019 ◽  
Author(s):  
Hui Zhao ◽  
Siqi Wang ◽  
Lixia Guo ◽  
Yanli Du ◽  
Linlin Liu ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Binding Sites ◽  
Prnp Gene ◽  
Post Transcriptional Regulation

scholarly journals Post-transcriptional regulation of MRTF-A by miRNAs during myogenic differentiation of myoblasts

2020 ◽  
Vol 48 (16) ◽  
pp. 8927-8942
Author(s):  
Ingo Holstein ◽  
Anurag Kumar Singh ◽  
Falk Pohl ◽  
Danny Misiak ◽  
Juliane Braun ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Mirna Expression ◽  
Binding Sites ◽  
Serum Response Factor ◽  
Myogenic Differentiation ◽  
Affinity Purification ◽  
Protein Abundance ◽  
Related Transcription Factor ◽  
Post Transcriptional Regulation ◽  
Serum Response

Abstract The differentiation and regeneration of skeletal muscle from myoblasts to myotubes involves myogenic transcription factors, such as myocardin-related transcription factor A (MRTF-A) and serum response factor (SRF). In addition, post-transcriptional regulation by miRNAs is required during myogenesis. Here, we provide evidence for novel mechanisms regulating MRTF-A during myogenic differentiation. Endogenous MRTF-A protein abundance and activity decreased during C2C12 differentiation, which was attributable to miRNA-directed inhibition. Conversely, overexpression of MRTF-A impaired differentiation and myosin expression. Applying miRNA trapping by RNA affinity purification (miTRAP), we identified miRNAs which directly regulate MRTF-A via its 3′UTR, including miR-1a-3p, miR-206-3p, miR-24-3p and miR-486-5p. These miRNAs were upregulated during differentiation and specifically recruited to the 3′UTR of MRTF-A. Concomitantly, Ago2 recruitment to the MRTF-A 3′UTR was considerably increased, whereas Dicer1 depletion or 3′UTR deletion elevated MRTF-A and inhibited differentiation. MRTF-A protein expression was inhibited by ectopic miRNA expression in murine C2C12 and primary human myoblasts. 3′UTR reporter activity diminished upon differentiation or miRNA expression, whereas deletion of the predicted binding sites reversed these effects. Furthermore, TGF-β abolished MRTF-A reduction and decreased miR-486-5p expression. Our findings implicate miR-24-3p and miR-486-5p in the repression of MRTF-A and suggest a complex network of transcriptional and post-transcriptional mechanisms regulating myogenesis.

scholarly journals Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs

2016 ◽  
Author(s):  
Marta Melé ◽  
Kaia Mattioli ◽  
William Mallard ◽  
David M Shechner ◽  
Chiara Gerhardinger ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Binding Sites ◽  
Transcriptional Repression ◽  
Tissue Specific ◽  
Dna And Rna ◽  
Evolutionarily Conserved ◽  
Specific Factors ◽  
The Stability ◽  
Post Transcriptional Regulation

ABSTRACTWhile long intergenic noncoding RNAs (lincRNAs) and mRNAs share similar biogenesis pathways, these transcript classes differ in many regards. LincRNAs are less evolutionarily conserved, less abundant, and more tissue-specific, suggesting that their pre‐ and post-transcriptional regulation is different from that of mRNAs. Here, we perform an in-depth characterization of the features that contribute to lincRNA regulation in multiple human cell lines. We find that lincRNA promoters are depleted of transcription factor (TF) binding sites, yet enriched for some specific factors such as GATA and FOS relative to mRNA promoters. Surprisingly, we find that H3K9me3—a histone modification typically associated with transcriptional repression—is more enriched at the promoters of active lincRNA loci than at those of active mRNAs. Moreover, H3K9me3-marked lincRNA genes are more tissue-specific. The most discriminant differences between lincRNAs and mRNAs involve splicing. LincRNAs are less efficiently spliced, which cannot be explained by differences in U1 binding or the density of exonic splicing enhancers, but may be partially attributed to lower U2AF65 binding and weaker splicing–related motifs. Conversely, the stability of lincRNAs and mRNAs is similar, differing only with regard to the location of stabilizing protein binding sites. Finally, we find that certain transcriptional properties are correlated with higher evolutionary conservation in both DNA and RNA motifs, and are enriched in lincRNAs that have been functionally characterized.

scholarly journals Genetic variants associated mRNA stability in lung

2021 ◽  
Author(s):  
Jian-Rong Li ◽  
Mabel Tang ◽  
Yafang Li ◽  
Christopher I Amos ◽  
Chao Cheng
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Mrna Stability ◽  
Genetic Variants ◽  
Binding Sites ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Seq ◽  
Post Transcriptional Regulation ◽  
Gene Expression Levels

AbstractExpression quantitative trait loci (eQTLs) analyses have been widely used to identify genetic variants associated with gene expression levels to understand what molecular mechanisms underlie genetic traits. The resultant eQTLs might affect the expression of associated genes through transcriptional or post-transcriptional regulation. In this study, we attempt to distinguish these two types of regulation by identifying genetic variants associated with mRNA stability of genes (stQTLs). Specifically, we computationally inferred mRNA stability of genes based on RNA-seq data and performed association analysis to identify stQTLs. Using the Genotype-Tissue Expression (GTEx) lung RNA-Seq data, we identified a total of 142,801 stQTLs for 3,942 genes and 186,132 eQTLs for 4,751 genes from 15,122,700 genetic variants for 13,476 genes, respectively. Interesting, our results indicated that stQTLs were enriched in the CDS and 3’UTR regions, while eQTLs are enriched in the CDS, 3’UTR, 5’UTR, and upstream regions. We also found that stQTLs are more likely than eQTLs to overlap with RNA binding protein (RBP) and microRNA (miRNA) binding sites. Our analyses demonstrate that simultaneous identification of stQTLs and eQTLs can provide more mechanistic insight on the association between genetic variants and gene expression levels.Author SummaryIn the past decade, many studies have identified genetic variants associated with gene expression level (eQTLs) in different phenotypes, including tissues and diseases. Gene expression is the result of cooperation between transcriptional regulation, such as transcriptional activity, and post-transcriptional regulation, such as mRNA stability. Here, we present a computational framework that take advantage of recently developed methods to estimate mRNA stability from RNA-Seq, which is widely used to estimate gene expression, and then to identify genetic variants associated with mRNA stability (stQTLs) in lung tissue. Compared to eQTLs, we found that genetic variants that affects mRNA stability are more significantly located in the CDS and 3’UTR regions, which are known to interact with RNA-binding proteins (RBPs) or microRNAs to regulate stability. In addition, stQTLs are significantly more likely to overlap the binding sites of RBPs. We show that the six RBPs that most significantly bind to stQTLs are all known to regulate mRNA stability. This pipeline of simultaneously identifying eQTLs and stQTLs using only RNA-Seq data can provide higher resolution than traditional eQTLs study to better understand the molecular mechanisms of genetic variants on the regulation of gene expression.

scholarly journals RADAR: annotation and prioritization of variants in the post-transcriptional regulome of RNA-binding proteins

2018 ◽  
Author(s):  
Jing Zhang ◽  
Jason Liu ◽  
Donghoon Lee ◽  
Jo-Jo Feng ◽  
Lucas Lochovsky ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Binding Sites ◽  
Rna Structure ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Network Centrality ◽  
Impact Score ◽  
Variant Prioritization ◽  
Post Transcriptional Regulation

AbstractRNA-binding proteins (RBPs) play key roles in post-transcriptional regulation and disease. Their binding sites cover more of the genome than coding exons; nevertheless, most noncoding variant-prioritization methods only focus on transcriptional regulation. Here, we integrate the portfolio of ENCODE-RBP experiments to develop RADAR, a variant-scoring framework. RADAR uses conservation, RNA structure, network centrality, and motifs to provide an overall impact score. Then it further incorporates tissue-specific inputs to highlight disease-specific variants. Our results demonstrate RADAR can successfully pinpoint variants, both somatic and germline, associated with RBP-function dysregulation, that cannot be found by most current prioritization methods, for example variants affecting splicing.

43-OR: Post-transcriptional Regulation of Slc16a1 mRNA Is Essential for Maintaining Normal ß-Cell Function

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 43-OR
Author(s):  
DINA MOSTAFA ◽  
AKINORI TAKAHASHI ◽  
TADASHI YAMAMOTO
Keyword(s):  
Transcriptional Regulation ◽  
Cell Function ◽  
Post Transcriptional Regulation
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