mRNA Stability

Abstract

The steady‐state level of a messenger ribonucleic acid (mRNA) is determined by both its rate of synthesis and degradation. The degradation of mRNA is an important tool employed by cells to control gene expression and to adjust the level of protein synthesis in response to physiological needs or environmental signals. The degradation of mRNA in all organisms is mastered by a rather restricted number of enzymes with major (endo‐ and exoribonucleases) and ancillary (e.g. RNA helicases) functions. Some of these enzymes are phylogenetically conserved across the three domains of life – bacteria, archaea and eukarya. Moreover, the main components of the RNA decay machinery can associate with each other to form multienzyme complexes, which enable to coordinate and control mRNA decay in vivo. This review provides a brief overview on the major factors and mechanisms involved in bacterial and eukaryal mRNA degradation.

Key Concepts:

  • The stability of individual mRNAs varies and is dependent on intrinsic properties (i.e. specific structure and sequence) of transcripts.

  • The enzymes and factors involved in mRNA decay in prokaryotes and eukaryotes can associate with each other to form multienzyme complexes such as degradosomes or exosomes

  • Mechanisms of mRNA decay in pro‐ and eukaryotes share many common steps.

  • Pro‐ and eukaryotic cells use specific mechanisms to eliminate defective mRNAs.

  • Numerous noncoding RNAs control mRNA decay in pro‐ and eukaryotes.

Keywords: mRNA decay; noncoding RNAs; RNases; RNA‐binding proteins

Figure 1.

General mRNA decay pathways in bacteria. (a) 3′ to 5′ directional pathway of bacterial mRNA decay by exoribonucleases. On addition of the poly(A) tail by PAPI, PNPase or RNase R can degrade the mRNA. (b) In E. coli, mRNA decay can be initiated by pyrophosphate removal, followed by endonucleolytic cleavage of the 5′‐monophosphate‐dependent RNase E. The resulting 5′ fragment is then degraded by 3′ to 5′ exonucleases like PNPase, RNase R or RNase II. On the first RNase E cleavage, the downstream fragment is endowed with a 5′‐monophosphate, which serves as a signal for the next endonucleolytic cut by RNase E. Repeated cycles of RNase E‐dependent endonucleolytic cleavages and exoribonucleolytic decay finally lead to 5′ to 3′ directional decay of the mRNA. The 3′ end of the mRNA containing a stem–loop structure might be first (i) polyadenylated by poly(A) polymerase I (PAPI) or (ii) partly unfolded by RhlB helicase, and then exonucleolytically degraded. As the PNPase‐ and RNase II‐mediated processing ultimately yields short oligonucleotides, their further conversion to mononucleotides is accomplished by oligoribonuclease (OligoRNase). (c) In B. subtilis, the major pathway of mRNA decay starts with pyrophosphate removal followed by endonucleolytic cleavage in the 5′ part of the mRNA by RNase Y. The resulting decay intermediates are further degraded by the concerted action of 3′ to 5′ (e.g. PNPase) and 5′ to 3′ (RNase J1) exonucleases. Alternatively, due to the presence of 5′ monophosphate, which serves as a signal for the 5′ to 3′ exoribonuclease activity of RNase J1, RNA decay can commence in 5′ to 3′ direction immediately after pyrophosphate removal (alternative pathway I). (d) In some cases, mRNA decay in B. subtilis is directly initiated by endonucleolytic cut made by RNase J1, and then the resulting intermediate products of decay are further degraded in the same manner as decay intermediates in the general pathway.

Figure 2.

Principal mRNA decay pathways in eukaryotes. (a) Following enzymatic removal of the 3′ poly(A) tail, the mRNA can be degraded by two mechanisms. (1) The exosome can degrade the mRNA in 3′ to 5′ direction and the remaining cap structure is then enzymatically hydrolysed by the Dcp1/Dcp2(Dcp) decapping enzyme (right). (2) Deadenylation can lead to assembly of the Pat1/Lsm1–7protein complex at the 3′ end of the transcript and to induction of decapping by DCP. On decapping, the mRNA can be degraded in 5′ to 3′ direction by an exoribonuclease, for example, XRN1 (left). (b) Schematically shown are the nonsense‐mediated decay (NMD), the nonstop decay (NSD) and the no‐go decay (NGD). For explanations, see text.

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Kaberdin, Vladimir, and Bläsi, Udo(Jul 2014) mRNA Stability. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000533.pub3]