Transfer RNA-derived fragments and tRNA halves: biogenesis, biological functions and their roles in diseases

Abstract

The number of studies on non-coding RNAs has increased substantially in recent years owing to their importance in gene regulation. However, the biological functions of small RNAs from abundant species of housekeeping non-coding RNAs (rRNA, tRNA, etc.) remain a highly studied topic. tRNA-derived small RNAs (tsRNAs) refer to the specific cleavage of tRNAs by specific nucleases [e.g., Dicer and angiogenin (ANG)] in particular cells or tissues or under certain conditions such as stress and hypoxia. tsRNAs are a type of non-coding small RNA that are widely found in the prokaryotic and eukaryotic transcriptomes and are generated from mature tRNAs or precursor tRNAs at different sites. There are two main types of tsRNAs, tRNA-derived fragments (tRFs) and tRNA halves. tRFs are 14-30 nucleotides (nt) long and mainly consist of three subclasses: tRF-5, tRF-3, and tRF-1. tRNA halves, which are 31-40 nt long, are generated by specific cleavage in the anticodon loops of mature tRNAs. There are two types of tRNA halves, 5'-tRNA halves and 3'-tRNA halves. tsRNAs have multiple biological functions including acting as signaling molecules in stress responses and as regulators of gene expression. Additionally, they have been considered to be involved in RNA processing, cell proliferation, translation suppression, the modulation of DNA damage response, and neurodegeneration. More importantly, they are closely related to the occurrence of many human diseases such as tumors, infectious diseases, metabolic diseases, and neurological diseases. Moreover, tsRNAs have the potential to become new biomarkers for disease diagnosis. Continuous investigations will help us to understand their generation and regulatory mechanisms as well as the possible roles of tRFs and tRNA halves.

ReCappable Seq: Comprehensive Determination of Transcription Start Sites derived from all RNA polymerases

“…Additionally, we found 3 novel TSS clustered at around -17, +7 and +40bp from the mature tRNA 5'end ( Figure 4a). The downstream TSS cluster at +40bp is consistent with the notion that tRNAs might have originated from tRNA halves [26]. Further refinement relative to the type of tRNA reveals that downstream TSS are mostly found in leu tRNA and lys tRNA ( Supplementary Figure 7).…”

The cellular landscape of mid‐size noncoding RNA

“…As the D-arm, anticodon arm, and finally the TΨC arm and the acceptor stem form, the maturation process terminates with 5 0 and 3 0 end trimming, the removal of introns, if present, and the addition of the characteristic CCA tails. At any point in this maturation pathway, posttranscriptional modifications can be added to influence folding (Belostotsky, Frishberg, & Entelis, 2012;Chatterjee, Nostramo, Wan, & Hopper, 2018;Fang & Guo, 2017;Shen et al, 2018;Wichtowska, Turowski, & Boguta, 2013). In contrast spliceosomal RNAs mature posttranscriptionally.…”

The tRNA‐associated dysregulation in immune responses and immune diseases

“…Typically, tRNAs in the cytoplasm have a length of 73-90 nucleotides, while mitochondrial tRNAs (mt-tRNAs) have only 57. 12 Generally, aminoacyl-tRNAs recognize 61 triplet codons in mRNAs and decode them into 20 standard amino acids in the translation machinery. 12 Generally, aminoacyl-tRNAs recognize 61 triplet codons in mRNAs and decode them into 20 standard amino acids in the translation machinery.…”

“…11 The mature tRNAs are characterized by a "clover" secondary structure with a D-loop, an anticodon loop, a variable loop, a T-loop and an acceptor arm, as well as an L-shaped tertiary structure maintained by hydrogen bonds. 12 Generally, aminoacyl-tRNAs recognize 61 triplet codons in mRNAs and decode them into 20 standard amino acids in the translation machinery. 13 Specially, suppressor tRNAs are molecules that bear mutations in the anticodon allowing a stop codon to be recognized as a regular codon, resulting in amino acid incorporation instead.…”