hnRNPs and ELAVL1 cooperate with uORFs to inhibit protein translation

Zhang, Jiewen; Kong, Lijuan; Guo, Si-chao; Bu, Meng-Meng; Guo, Qin; Zhu, Na; Qiu, Chuan; Yan, Xuejing; Chen, Qian; Zhang, Hongfei; Zhuang, Junling; Wang, Qiong; Zhang, Samuel S.; Shen, Yan; Chen, Meihong

doi:10.1093/nar/gkw991

Cited by 18 publications

(21 citation statements)

References 39 publications

(44 reference statements)

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“…HnRNPA2B1 is a protein involved in the translocation of RNA molecules within the cell (Munro et al 1999) and from viral particles (Lévesque et al 2006). Also, members of the same family of RNPs are involved in the binding of mRNAs (Suzuki and Matsuoka 2017) and can regulate gene transcription (Zhang et al 2017). SYNCRIP, another member of the hnRNP family, is a known splicing factor (Beuck et al 2016), which is also involved in viral RNA replication (Choi et al 2004;Liu et al 2009) that also binds to mRNA (Kuchler et al 2014) and that has an important role in mRNA transcription and degradation (Moser et al 2007;Duning et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Exploring the RNA landscape of endothelial exosomes

Pérez-Boza

Lion

Struman

2017

RNA

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Exosomes are small extracellular vesicles of around 100 nm of diameter produced by most cell types. These vesicles carry nucleic acids, proteins, lipids, and other biomolecules and function as carriers of biological information in processes of extracellular communication. The content of exosomes is regulated by the external and internal microenvironment of the parent cell, but the intrinsic mechanisms of loading of molecules into exosomes are still not completely elucidated. In this study, by the use of next-generation sequencing we have characterized in depth the RNA composition of healthy endothelial cells and exosomes and provided an accurate profile of the different coding and noncoding RNA species found per compartment. We have also discovered a set of unique genes preferentially included (or excluded) into vesicles. Moreover, after studying the enrichment of RNA motifs in the genes unequally distributed between cells and exosomes, we have detected a set of enriched sequences for several classes of RNA. In conclusion, our results provide the basis for studying the involvement of RNA-binding proteins capable of recognizing RNA sequences and their role in the export of RNAs into exosomes.

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Section: Discussionmentioning

confidence: 99%

Exploring the RNA landscape of endothelial exosomes

Pérez-Boza

Lion

Struman

2017

RNA

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“…A complex mechanism sees HNRNPA0, HNRNPA2B1, and ELAVL1 concurrently binding to the 5′UTR of ANXA2R mRNA. They focus the translation on its first uORF, thus tightly inhibiting the synthesis of the downstream coding sequence (Zhang et al, 2016 ). Another 5′UTR-mediated RNA-dependent interaction occurs between DDX3X and CAPRIN1.…”

Section: Cooperative Target Regulationmentioning

confidence: 99%

Handshakes and Fights: The Regulatory Interplay of RNA-Binding Proteins

Dassi

2017

Front. Mol. Biosci.

122

102

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What drives the flow of signals controlling the outcome of post-transcriptional regulation of gene expression? This regulatory layer, presiding to processes ranging from splicing to mRNA stability and localization, is a key determinant of protein levels and thus cell phenotypes. RNA-binding proteins (RBPs) form a remarkable army of post-transcriptional regulators, strong of more than 1,500 genes implementing this expression fine-tuning plan and implicated in both cell physiology and pathology. RBPs can bind and control a wide array of RNA targets. This sheer amount of interactions form complex regulatory networks (PTRNs) where the action of individual RBPs cannot be easily untangled from each other. While past studies have mostly focused on the action of individual RBPs on their targets, we are now observing an increasing amount of evidence describing the occurrence of interactions between RBPs, defining how common target RNAs are regulated. This suggests that the flow of signals in PTRNs is driven by the intertwined contribution of multiple RBPs, concurrently acting on each of their targets. Understanding how RBPs cooperate and compete is thus of paramount importance to chart the wiring of PTRNs and their impact on cell phenotypes. Here we review the current knowledge about patterns of RBP interaction and attempt at describing their general principles. We also discuss future directions which should be taken to reach a comprehensive understanding of this fundamental aspect of gene expression regulation.

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“…Cold Spring Harbor Laboratory Press on May 9, 2018 -Published by genome.cshlp.org Downloaded from 2011; Schleich et al 2014;Zhang et al 2017). We investigated protein occupancy around the translation initiation site (TIS) of uORFs using genome-wide cross-linked protein occupancy data (gPAR-CLIP) ( Fig.…”

Section: Wwwgenomeorgmentioning

confidence: 99%

Conserved non-AUG uORFs revealed by a novel regression analysis of ribosome profiling data

et al. 2017

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Upstream open reading frames (uORFs), located in transcript leaders (5′ UTRs), are potent cis-acting regulators of translation and mRNA turnover. Recent genome-wide ribosome profiling studies suggest that thousands of uORFs initiate with non-AUG start codons. Although intriguing, these non-AUG uORF predictions have been made without statistical control or validation; thus, the importance of these elements remains to be demonstrated. To address this, we took a comparative genomics approach to study AUG and non-AUG uORFs. We mapped transcription leaders in multiple Saccharomyces yeast species and applied a novel machine learning algorithm (uORF-seqr) to ribosome profiling data to identify statistically significant uORFs. We found that AUG and non-AUG uORFs are both frequently found in Saccharomyces yeasts. Although most non-AUG uORFs are found in only one species, hundreds have either conserved sequence or position within Saccharomyces. uORFs initiating with UUG are particularly common and are shared between species at rates similar to that of AUG uORFs. However, non-AUG uORFs are translated less efficiently than AUG-uORFs and are less subject to removal via alternative transcription initiation under normal growth conditions. These results suggest that a subset of non-AUG uORFs may play important roles in regulating gene expression.

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hnRNPs and ELAVL1 cooperate with uORFs to inhibit protein translation

Cited by 18 publications

References 39 publications

Exploring the RNA landscape of endothelial exosomes

Exploring the RNA landscape of endothelial exosomes

Handshakes and Fights: The Regulatory Interplay of RNA-Binding Proteins

Conserved non-AUG uORFs revealed by a novel regression analysis of ribosome profiling data

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