The Interplay between the RNA Decay and Translation Machinery in Eukaryotes

Heck, Adam M.; Wilusz, Jeffrey

doi:10.1101/cshperspect.a032839

Cited by 59 publications

(49 citation statements)

References 213 publications

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“…Such mRNA stabilization ampli es the positive effect of high initiation rate on protein expression 5,6 . Thus, ef cient initiation is widely associated with increased mRNA stability and higher protein expression [7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

Inverted translational control of eukaryotic gene expression by ribosome collisions

Park

Subramaniam

2019

Preprint

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The canonical model of eukaryotic translation posits that ef cient translation initiation increases protein expression and mRNA stability. Contrary to this dogma, we show that increasing initiation rate can decrease both protein expression and stability of certain mRNAs in the budding yeast, S. cerevisiae. These mRNAs contain a stretch of poly-basic residues that cause ribosome stalling. Using computational modeling, we predict that the observed decrease in gene expression at high initiation rates occurs when ribosome collisions at stalls stimulate abortive termination of the leading ribosome and cause endonucleolytic mRNA cleavage. We test our prediction by identifying critical roles for the collision-associated quality control factors, Asc1 and Hel2 (RACK1 and ZNF598 in humans, respectively). Remarkably, hundreds of S. cerevisiae mRNAs that contain ribosome-stall sequences also exhibit lower translation ef ciency. We propose that these mRNAs have undergone evolutionary selection for inef cient initiation to escape collision-stimulated reduction in gene expression.

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Section: Introductionmentioning

confidence: 99%

Inverted translational control of eukaryotic gene expression by ribosome collisions

Park

Subramaniam

2019

Preprint

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“…In cases of faulty mRNAs that are degraded due to a lack of a TC (nonstop decay) or due to a strong secondary structure or the absence of a cognate tRNA (no-go decay), the activating signal is the ribosome stalling during elongation. In this scenario, ribosome stalling marks a dead-end event and the rescue of an otherwise trapped ribosome is crucial (reviewed in 17,43,44 ). The term "stalling" is used broadly to describe increased ribosome density, without distinguishing between transient pauses and stable stalls.…”

Section: Discussionmentioning

confidence: 99%

Human NMD ensues independently of stable ribosome stalling

Karousis

Gurzeler

Annibaldis

et al. 2019

Preprint

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Nonsense-mediated mRNA decay (NMD) is a translation-dependent RNA degradation pathwaythat is important for the elimination of faulty and the regulation of normal mRNAs. The molecular details of the early steps in NMD are not fully understood but previous work suggests that NMD activation occurs as a consequence of ribosome stalling at the termination codon (TC). To test this hypothesis, we established an in vitro translation-coupled toeprinting assay based on lysates from human cells that allows monitoring of ribosome occupancy at the TC of reporter mRNAs. In contrast to the prevailing NMD model, our in vitro system revealed similar ribosomal occupancy at the stop codons of NMD-sensitive and NMD-insensitive reporter mRNAs.Moreover, ribosome profiling revealed a similar density of ribosomes at the TC of endogenous NMD-sensitive and NMD-insensitive mRNAs in vivo. Together, these data show that NMD activation is not accompanied by stable stalling of ribosomes at TCs.

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“…Other cytoplasmic RNA decay mechanisms also exist, including nonsense‐mediated decay (NMD; further described below in Section 3.2), no‐go decay (Doma & Parker, ) and nonstop decay (Frischmeyer et al, ; van Hoof, Frischmeyer, Dietz, & Parker, ). To note, much of the work that has been done to elucidate these pathways has come primarily from S. cerevisiae (Huch & Nissan, ; for a more comprehensive review on the detailed mechanisms governing RNA decay pathways, see Heck & Wilusz, ; Labno et al, ; Parker, ).…”

Section: Autophagy Regulation By Rna Decaymentioning

confidence: 99%

On the edge of degradation: Autophagy regulation by RNA decay

Delorme-Axford

Klionsky

2018

WIREs RNA

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Cells must dynamically adapt to altered environmental conditions, particularly during times of stress, to ensure their ability to function effectively and survive. The macroautophagy/autophagy pathway is highly conserved across eukaryotic cells and promotes cell survival during stressful conditions. In general, basal autophagy occurs at a low level to sustain cellular homeostasis and metabolism. However, autophagy is robustly upregulated in response to nutrient deprivation, pathogen infection and increased accumulation of potentially toxic protein aggregates and superfluous organelles. Within the cell, RNA decay maintains quality control to remove aberrant transcripts and regulate appropriate levels of gene expression. Recent evidence has identified components of the cellular mRNA decay machinery as novel regulators of autophagy. Here, we review current findings that demonstrate how autophagy is modulated through RNA decay. This article is categorized under: RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Turnover and Surveillance > Regulation of RNA Stability K E Y W O R D S Dcp2, DDX6, Dhh1, mRNA decay, RNA degradation, vacuole, Xrn1/XRN1, yeast 1 | INTRODUCTION 1.1 | OverviewWhen encountering altered environments and fluctuating nutrient conditions, cells must respond and adapt through mechanisms that support their survival. Autophagy is a precisely controlled catabolic process of cellular "self-eating" that is highly conserved across eukaryotes (from yeast to human). Starvation, pathogen infection and/or the accumulation of damaged or superfluous organelles can activate the autophagy pathway, which enables eukaryotic cells to function and survive amid stress conditions. Autophagy also removes harmful cellular material, while at the same time providing a source of macromolecules to sustain cellular metabolism during low-energy periods. The de novo formation of the sequestering phagophore, which matures into a double-membrane autophagosome is the characteristic morphological feature of autophagy. At present, 42 autophagy-related (ATG) genes have been identified in fungi; many of these genes have homologs or at least functional counterparts in higher eukaryotes. Autophagy is primarily a degradative pathway requiring the vacuole (in yeast or plants) or lysosomes (in metazoans) for the breakdown of sequestered cargo. However, the biosynthetic cytoplasm-to-vacuole targeting (Cvt) pathway utilizes most of Abbreviations: ATG, autophagy-related; CPA, cleavage and polyadenylation; Cvt, cytoplasm-to-vacuole targeting; GABARAP, GABA type A receptorassociated protein; MAP1LC3/ LC3, microtubule associated protein 1 light chain 3; miRNA, microRNA; mRNA, messenger RNA; MTOR, mechanistic target of rapamycin kinase;

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The Interplay between the RNA Decay and Translation Machinery in Eukaryotes

Cited by 59 publications

References 213 publications

Inverted translational control of eukaryotic gene expression by ribosome collisions

Inverted translational control of eukaryotic gene expression by ribosome collisions

Human NMD ensues independently of stable ribosome stalling

On the edge of degradation: Autophagy regulation by RNA decay

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