tiRNAs

tiRNAs, short for tRNA-derived stress-induced RNAs, are a class of small noncoding RNAs generated from transfer RNA (tRNA) during cellular stress. They are distinct from random tRNA degradation products and are considered functional regulatory RNAs. TiRNAs typically range from about 28 to 40 nucleotides and are categorized based on origin: 5'-tiRNAs originate from the 5' end of a mature tRNA, while 3'-tiRNAs come from the 3' end.

Biogenesis and structure: In response to stress, ribonucleases such as angiogenin cleave tRNAs in or near the anticodon loop, producing tRNA halves. The resulting 5'-tiRNA and 3'-tiRNA fragments can accumulate in the cytoplasm and participate in regulatory processes. Many 5'-tiRNAs carry a 5'-phosphate and a 2',3'-cyclic phosphate at the 3' end; some 5'-tiRNAs contain a terminal oligoguanine motif (5'-TOG) that influences protein interactions and localization to stress granules.

Functions: A central role attributed to tiRNAs is the suppression of global translation during stress. 5'-tiRNAs can disrupt the formation of the eIF4F complex at the mRNA cap and promote assembly of stress granules, thereby reducing protein synthesis. 3'-tiRNAs may regulate gene expression through other interactions. tiRNAs can bind RNA-binding proteins such as YB-1, and in some reports may associate with Argonaute proteins, suggesting possible microRNA-like activities, though such roles are not uniformly demonstrated across systems.

Physiological relevance: TiRNAs are conserved across eukaryotes and have been studied in contexts such as cellular stress responses, cancer, and neurodegenerative diseases. They are typically detected by small RNA sequencing or northern blotting and are considered part of the broader family of tRNA-derived fragments (tRFs), which also includes other stress-responsive species.