Controlling translation via modulation of tRNA levels

Transfer RNAs (tRNAs) are critical adaptor molecules that carry amino acids to a messenger RNA (mRNA) template during protein synthesis. Although tRNAs have commonly been viewed as abundant ‘house‐keeping’ RNAs, it is becoming increasingly clear that tRNA expression is tightly regulated. Depending on a cell's proliferative status, the pool of active tRNAs is rapidly changed, enabling distinct translational programs to be expressed in differentiated versus proliferating cells. Here, I highlight several post‐transcriptional regulatory mechanisms that allow the expression or functions of tRNAs to be altered. Modulating the modification status or structural stability of individual tRNAs can cause those specific tRNA transcripts to selectively accumulate or be degraded. Decay generally occurs via the rapid tRNA decay pathway or by the nuclear RNA surveillance machinery. In addition, the CCA‐adding enzyme plays a critical role in determining the fate of a tRNA. The post‐transcriptional addition of CCA to the 3′ ends of stable tRNAs generates the amino acid attachment site, whereas addition of CCACCA to unstable tRNAs prevents aminoacylation and marks the tRNA for degradation. In response to various stresses, tRNAs can accumulate in the nucleus or be further cleaved into small RNAs, some of which inhibit translation. By implementing these various post‐transcriptional control mechanisms, cells are able to fine‐tune tRNA levels to regulate subsets of mRNAs as well as overall translation rates. WIREs RNA 2015, 6:453–470. doi: 10.1002/wrna.1287