Transfer RNA Synthesis and Regulation

Abstract

Abstract Transfer ribonucleic acid (tRNA) , which is primarily transcribed from tRNA genes by RNA polymerase, matures via several steps: processing, splicing, CCA addition and post‐transcriptional modifications. Primary transcripts of tRNA genes contain extra 5′ and 3′ sequences, which are removed by a set of nucleases. In addition, some primary transcripts contain introns, which are spliced out by specific endonucleases or in self‐splicing reactions. The ligation of exons generally requires a tRNA ligase. In some species, the CCA sequences present at the 3′‐termini of all mature tRNAs are not encoded in the tRNA genes, but are added post‐transcriptionally by a CCA‐adding enzyme. All mature tRNA molecules contain modified nucleotides, generated by specific tRNA modification enzymes or guide RNA systems. These modified nucleotides are involved in stabilisation of tRNA structure, decoding, tRNA quality control, regulation of subcellular localisation of tRNAs and immune responses against infectious organisms. Key Concepts: tRNA is transcribed from tRNA genes by RNA polymerase, and matures through processing, splicing, CCA addition and post‐transcriptional modification. Synthesis of tRNA is regulated by promoter activity and specific factors (ppGpp and/or pppGpp in prokaryotes, and Maf1 in eukaryotes), depending on the nutrient conditions of the cell. The relative amounts of tRNA are regulated by several factors: copy number of tRNA genes, transcriptional activity, and degradation by various nucleases. Primary transcripts of tRNA genes contain extra 5′ and 3′ sequences, which are removed by a set of nucleases. In some cases, tRNA transcripts contain introns, which are spliced out by specific endonuclease or the group I intron reaction. The two resultant fragments are joined by RNA ligase or the self‐splicing reaction. CCA‐adding enzyme regulates the amount of active tRNA by introducing the CCA sequence at the C ‐terminus of tRNA. tRNA possesses a variety of modified nucleotides, which are introduced by specific tRNA modification enzymes. Several modifications of tRNA play important roles in the translation process: promotion, expansion, restriction, and/or alteration of codon–anticodon interactions; stabilisation of tRNA structure; recognition by translation factors and aminoacyl‐tRNA synthetases; etc. Several modified nucleotides in tRNA are involved in RNA quality control systems, regulation of tRNA transport, infection and immune responses.