Connections Underlying Translation and mRNA Stability.
Gene expression and regulation in organisms minimally depends on transcription by RNA polymerase and on the stability of the RNA product (for both coding and non-coding RNAs). For coding RNAs, gene expression is further influenced by the amount of translation by the ribosome and by the stability of the protein product. The stabilities of these two classes of RNA, non-coding and coding, vary considerably: tRNAs and rRNAs tend to be long lived while mRNAs tend to be more short lived. Even among mRNAs, however, there is a considerable range in stability (ranging from seconds to hours in bacteria and up to days in metazoans), suggesting a significant role for stability in the regulation of gene expression. Here, we review recent experiments from bacteria, yeast and metazoans indicating that the stability of most mRNAs is broadly impacted by the actions of ribosomes that translate them. Ribosomal recognition of defective mRNAs triggers "mRNA surveillance" pathways that target the mRNA for degradation [Shoemaker and Green (2012) ]. More generally, even the stability of perfectly functional mRNAs appears to be dictated by overall rates of translation by the ribosome [Herrick et al. (1990), Presnyak et al. (2015) ]. Given that mRNAs are synthesized for the purpose of being translated into proteins, it is reassuring that such intimate connections between mRNA and the ribosome can drive biological regulation. In closing, we consider the likelihood that these connections between protein synthesis and mRNA stability are widespread or whether other modes of regulation dominate the mRNA stability landscape in higher organisms.
Program in Molecular Biophysics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Department of Molecular Biology and Genetics, Baltimore, MD 21205, USA.
Aditya
A
Radhakrishnan
Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Department of Molecular Biology and Genetics, Baltimore, MD 21205, USA. Electronic address: ragreen@jhmi.edu.
Rachel
R
Green
D000818:Animals; D001419:Bacteria / Q000235:genetics; D005786:Gene Expression Regulation; D014176:Protein Biosynthesis; D020871:RNA Stability; D012441:Saccharomyces cerevisiae / Q000235:genetics
codon optimality; mRNA decay; mRNA surveillance; microRNAs