tsRNAs

tsRNAs are small non-coding RNAs derived from transfer RNAs (tRNAs). They include two main classes: tRNA-derived fragments (tRFs) and tRNA-derived stress-induced RNAs (tiRNAs). tRFs originate from portions of mature tRNAs and are categorized by origin, such as tRF-5 from the 5′ end and tRF-3 from the 3′ end; tRF-1 derives from the 3′ trailer of precursor tRNA. tiRNAs are stress-induced halves produced by cleavage in the anticodon loop, yielding 5′-tiRNA and 3′-tiRNA species. Their lengths typically range from about 14 to 40 nucleotides depending on class and processing.

Biogenesis involves several ribonucleases, with activity that varies by organism and condition. Angiogenin, a stress-activated RNase, generates tiRNAs, while other enzymes such as Dicer, RNase Z/ELAC2, and RNase T2 contribute to tRF production in various contexts. The exact pathways and abundances are influenced by tissue type and cellular state.

Functions attributed to tsRNAs include regulation of gene expression and translation. Some tsRNAs associate with Argonaute proteins and can participate in miRNA-like silencing, whereas others influence translation initiation or ribosome assembly. They can bind RNA-binding proteins to affect mRNA stability, localization, and translation, and may promote stress granule formation. Additional roles have been described in transposon silencing, development, and disease, though mechanisms remain under investigation.

tsRNAs are found across eukaryotes, including humans, with expression patterns that are tissue- and condition-dependent. Research explores their potential as biomarkers and therapeutic targets. Sequencing tsRNAs is technically challenging due to tRNA modifications, which has driven the development of specialized library preparation and mapping approaches.