Abstract
Transfer tRNAs (tRNAs) are small non-coding RNAs that are highly conserved in all kingdoms of life. Originally discovered as the molecules that deliver amino acids to the growing polypeptide chain during protein synthesis, tRNAs have been believed for a long time to play exclusive role in translation. However, recent studies have identified key roles for tRNAs and tRNA-derived small RNAs in multiple other processes, including regulation of transcription and translation, posttranslational modifications, stress response, and disease. These emerging roles suggest that tRNAs may be central players in the complex machinery of biological regulatory pathways. Here we overview these non-canonical roles of tRNA in normal physiology and disease, focusing largely on eukaryotic and mammalian systems.
Highlights
Transfer RNAs are adaptor molecules that translate genetic information into protein sequence by delivering amino acids to the protein synthesis machinery during translation
Transfer RNAs are synthesized as precursors by RNA polymerase III (PolIII) and undergo a multistep maturation process, involving removal of the 5 leader, trimming of the 3 trailer, splicing of introns, modifications of nucleotides, and addition of the 3 terminal CCA tail that serves as a site for amino acid charging (Figure 1A)
After processing of pre-Transfer RNAs (tRNAs) in the nucleoplasm, mature tRNAs are transported to the cytoplasm through the nuclear pore complexes, which serve as quality control to ensure that only correctly processed tRNAs can pass into the cytoplasm (Chatterjee et al, 2018)
Summary
Transfer RNAs (tRNAs) are adaptor molecules that translate genetic information into protein sequence by delivering amino acids to the protein synthesis machinery during translation. Mature tRNAs, formed from pre-tRNA through specialized steps of cleavage and posttranscriptional modifications (Figure 1A), are 73–93 nucleotides (nt) in length. Their secondary structure resembles a cloverleaf shape with four stem-loops: the acceptor stem where the amino acid is attached, the anticodon loop containing the anticodon triplet that recognizes the specific complementary codons on mRNA during protein synthesis, the deoxyuridine stem-loop (D-arm), the T C stem-loop (T-arm), and the variable loop (V-loop) (Giege, 2008; Figure 1B). Transfer RNAs are synthesized as precursors by RNA polymerase III (PolIII) and undergo a multistep maturation process, involving removal of the 5 leader, trimming of the 3 trailer, splicing of introns, modifications of nucleotides, and addition of the 3 terminal CCA tail that serves as a site for amino acid charging (Figure 1A). Mature tRNAs are aminoacylated by their cognate aminoacyl-tRNA synthetases (aaRSs) (Berg and Offengand, 1958), which enables them to deliver the attached amino acids to the ribosome for incorporation into the growing polypeptide chain
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