The roles of the exoribonucleases DIS3L2 and XRN1 in human disease

Pashler, Amy L.; Towler, Benjamin P.; Jones, Christopher I.; Newbury, Sarah F.

doi:10.1042/bst20160107

Cited by 33 publications

(22 citation statements)

References 60 publications

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“…DIS3L2 preferentially recognizes mRNAs with short poly(U)-tracts at their 3 0 end that are added by poly(U) polymerases (PUPs) like TUT4/7 (Viegas et al 2015). Intriguingly, DIS3L2 has been linked to apoptosis (Thomas et al 2015), and mutations in DIS3L2 are associated with Perlman syndrome (Pashler et al 2016). These observations further underscore the biological and developmental importance of this 3 0 -to-5 0 exoribonuclease.…”

Section: The Major Steps and Mechanisms Of Mrna Decay In Eukaryotesmentioning

confidence: 85%

The Interplay between the RNA Decay and Translation Machinery in Eukaryotes

Heck

Wilusz

2018

Cold Spring Harb Perspect Biol

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RNA decay plays a major role in regulating gene expression and is tightly networked with other aspects of gene expression to effectively coordinate post-transcriptional regulation. The goal of this work is to provide an overview of the major factors and pathways of general messenger RNA (mRNA) decay in eukaryotic cells, and then discuss the effective interplay of this cytoplasmic process with the protein synthesis machinery. Given the transcript-specific and fluid nature of mRNA stability in response to changing cellular conditions, understanding the fundamental networking between RNA decay and translation will provide a foundation for a complete mechanistic understanding of this important aspect of cell biology.

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Section: The Major Steps and Mechanisms Of Mrna Decay In Eukaryotesmentioning

confidence: 85%

The Interplay between the RNA Decay and Translation Machinery in Eukaryotes

Heck

Wilusz

2018

Cold Spring Harb Perspect Biol

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“…Xrn1/XRN1 has been associated with human pathologies such as osteosarcoma and infectious diseases [80,81] and even virus infection in yeast [82,83]. Thus, the cell must strictly modulate autophagy at multiple levels to prevent disease pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

The exoribonuclease Xrn1 is a post-transcriptional negative regulator of autophagy

et al. 2018

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Macroautophagy/autophagy is a conserved catabolic process that promotes survival during stress. Autophagic dysfunction is associated with pathologies such as cancer and neurodegenerative diseases. Thus, autophagy must be strictly modulated at multiple levels (transcriptional, post-transcriptional, translational and post-translational) to prevent deregulation. Relatively little is known about the post-transcriptional control of autophagy. Here we report that the exoribonuclease Xrn1/XRN1 functions as a negative autophagy factor in the yeast Saccharomyces cerevisiae and in mammalian cells. In yeast, chromosomal deletion of XRN1 enhances autophagy and the frequency of autophagosome formation. Loss of Xrn1 results in the upregulation of autophagy-related (ATG) transcripts under nutrient-replete conditions, and this effect is dependent on the ribonuclease activity of Xrn1. Xrn1 expression is regulated by the yeast transcription factor Ash1 in rich conditions. In mammalian cells, siRNA depletion of XRN1 enhances autophagy and the replication of 2 picornaviruses. This work provides insight into the role of the RNA decay factor Xrn1/XRN1 as a post-transcriptional regulator of autophagy.

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“…While XRN1 is described as a general decay factor, there is evidence that 5' decay shows some specificity in vivo. Indeed, in Drosophila, mutations in XRN1 have specific phenotypes, including wound healing, epithelial closure and stem cell renewal in testes, suggesting that it specifically degrades a subset of mRNAs [51]. Most importantly, a recent study showed that yeast XRN1 associates with ribosomes and decays mRNAs during translation [52].…”

Section: Distinct Decay Pathwaysmentioning

confidence: 99%

GC content shapes mRNA decay and storage in human cells

Courel

Clément

Foretek

et al. 2018

Preprint

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Control of protein expression results from the fine tuning of mRNA synthesis, decay and translation. These processes, which are controlled by a large number of RNA-binding proteins and by localization in RNP granules such as P-bodies, appear often intimately linked although the rules of this interplay are not well understood. In this study, we combined our recent P-body transcriptome with various transcriptomes obtained following silencing of broadly acting mRNA decay and repression factors. This analysis revealed the central role of GC content in mRNA fate, in terms of P-body localization, mRNA translation and mRNA decay. It also rationalized why PBs mRNAs have a strikingly low protein yield. We report too the existence of distinct mRNA decay pathways with preference for AU-rich or GC-rich transcripts. Compared to this impact of the GC content, sequence-specific RBPs and miRNAs appeared to have only modest additional effects on their bulk targets. Altogether, these results lead to an integrated view of post-transcriptional control in human cells where most regulation at the level of translation is dedicated to AU-rich mRNAs, which have a limiting protein yield, whereas regulation at the level of 5' decay applies to GC-rich mRNAs, whose translation is optimal.

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The roles of the exoribonucleases DIS3L2 and XRN1 in human disease

Cited by 33 publications

References 60 publications

The Interplay between the RNA Decay and Translation Machinery in Eukaryotes

The Interplay between the RNA Decay and Translation Machinery in Eukaryotes

The exoribonuclease Xrn1 is a post-transcriptional negative regulator of autophagy

GC content shapes mRNA decay and storage in human cells

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