Translation Control by RNA

Abstract

Abstract Translation control by ribonucleic acid (RNA) refers to the process by which protein synthesis is regulated by structural elements in RNA (primary, secondary or tertiary), often cis ‐acting in the messenger RNA encoding the protein being synthesised, and also trans ‐acting in a number of systems. This article covers the historical early recognition of translation control by RNA in the RNA bacteriophage and extends the concept to include many additional examples of secondary structure control, or ‘riboswitches’, and other methods of controlling access by ribosomes to messenger ribonucleic acid (mRNA), including the role of small regulatory RNAs. Effects of RNA primary sequences on translation are also covered, including initiation signals, recoding (e.g. translational frameshifts), codon bias, translational attenuation and antisense regulation. mRNA stability is also considered, as well as an RNA‐based mechanism to facilitate translation termination, transfer‐messenger ribonucleic acid (tmRNA). Key Concepts mRNA secondary/tertiary structure can obscure or expose translation start sites and can be altered by conditions in the cell to regulate translation initiation (riboswitches). Translational coupling requires translation of an upstream gene before ribosomes can translate the downstream gene. Often used to promote equimolar levels of proteins that are utilised in comparable amounts (enzyme subunits), or for inhibition of more than one gene in an operon (ribosomal protein operons). Small RNAs, generally antisense RNA, can bind to mRNA to inhibit translation starts, or in some cases, to facilitate translation starts. Often requires a protein chaperone‐like Hfq. Antisense RNAs often lead to degradation of the RNA target. In eukaryotes, this is termed ‘ribonucleic acid interference’ (RNAi). Primary sequences in mRNA can also affect translation efficiency, including choice of start codon, or quality of the ribosome‐binding site, or as a target for a repressor protein (translational ‘operators’). Primary sequences in mRNA can in some instances trigger ‘recoding’, in which the mRNA is translated in an unexpected way, such as causing translational frameshifts, or incorporation of selenocysteine in response to a UGA codon. In the phenomenon of ‘translational attenuation’, the primary sequence encodes an inhibitory peptide that potentiates the ribosome to be inhibited by otherwise sub‐lethal concentrations of antibiotic, thereby exposing a downstream translation start for the antibiotic resistance gene. Codon bias can affect the efficiency of translation, where common codons in a given organism are almost exclusively used for highly expressed proteins, and rare codons for that organism used at a much higher frequency in poorly expressed proteins. Usually correlates to cognate tRNA levels. mRNA stability is a determinant of the amount of protein expressed; stability can be affected by both cis ‐ and trans ‐acting elements. tmRNA (transfer‐messenger ribonucleic acid) is a mechanism in bacteria for orderly termination of translation when there is a vacant A site on the ribosome.