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Review
. 2018 May 1;10(5):a032839.
doi: 10.1101/cshperspect.a032839.

The Interplay between the RNA Decay and Translation Machinery in Eukaryotes

Adam M Heck  1   2 , Jeffrey Wilusz  1   2
Affiliations
Review

The Interplay between the RNA Decay and Translation Machinery in Eukaryotes

Adam M Heck et al. Cold Spring Harb Perspect Biol. .

Abstract

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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Figures

Figure 1.
Figure 1.
The multiple pathways for exonucleases to gain access to RNAs targeted for degradation. 5′-3′ exoribonucleases (XRN1) require a 5′ monophosphate, whereas 3′-5′ exoribonucleases (exosome and DIS3L2) require an accessible 3′ hydroxyl. A 5′ monophosphate can be generated in a regulated fashion by the process of decapping, which can be deadenylation (poly(A) tail shortening) dependent or deadenylation independent. Deadenylation itself generates an accessible 3′ hydroxyl for exoribonucleases. Poly(U) polymerases (also called TUTases) can uridylate the 3′ end of RNA targets to increase DIS3L2 exonuclease accessibility. In the 3′-5′ exonuclease pathway, the scavenger decapping enzyme DCPS acts on short capped oligonucleotides to promote full degradation. Finally, rather than remodeling the natural 5′ and 3′ ends of the target mRNA, endoribonucleases, including the RNA-induced silencing complex (RISC) complex of the RNA interference (RNAi) pathway, can cleave a transcript internally and generate fragments with 5′ monophosphate and 3′ hydroxyl ends for exonucleolytic decay.
Figure 2.
Figure 2.
Numerous regulatory points exist throughout the transcript to modulate co-translational messenger RNA (mRNA) decay. A brief overview of the factors and the location on the transcript that can influence the rate of mRNA decay in association with ribosome loading, elongation, and termination. In the 5′ untranslated region (UTR) (green), RNA structure, initiation rates, and RNA-binding protein (RBP)/RNA factors acting in trans can co-regulate mRNA decay and translation. As ribosomes (blue) read through the open reading frame (ORF) (black), elongation speed or lack thereof (ribosome pausing) is the primary feature that links active translation and mRNA decay. Events such as premature termination, RNA modification, or protein/RNA trans factor interaction can alter ribosomal speed, thus influencing mRNA stability. Finally, the 3′ UTR (red) can modulate mRNA decay and translation via interactions with other protein/RNA factors, different 3′ UTR isoforms that can arise by alternative polyadenylation (APA), or via improper termination, which can result from a defective ribosome or lack of a stop codon. The cell uses all of these regulatory mechanisms to ensure that accurate and efficient translation is achieved.
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