tiRNA

tiRNA, short for tRNA-derived stress-induced RNA, refers to a class of small non-coding RNAs generated from mature transfer RNAs in response to cellular stress. Most tiRNAs are 28–36 nucleotides long and arise from cleavage in or near the anticodon loop, producing distinct 5' tiRNA and 3' tiRNA fragments, collectively called tRNA halves. TiRNA is sometimes used to describe the broader set of tRNA-derived fragments (tRFs) produced under stress, but in common usage it denotes stress-generated halves.

Biogenesis and enzymes: Under stress conditions such as oxidative stress, nutrient deprivation, heat shock, and UV exposure, ribonucleases cleave tRNAs at the anticodon loop. Angiogenin (ANG) is the best characterized enzyme responsible for generating tiRNAs in many animal and higher eukaryotic cells; other nucleases can contribute in different organisms or contexts. Production is rapid and cytoplasmic; tiRNAs may accumulate and signal the cellular stress state.

Functional aspects: 5' tiRNAs can interfere with translation initiation by displacing initiation factors (for example, components of the eIF4F complex) and promoting assembly of stress granules, thereby repressing global protein synthesis during stress. 3' tiRNAs may have distinct or overlapping regulatory roles, including potential effects on RNA stability and interactions with RNA-binding proteins. The precise targets and mechanisms appear to be sequence- and context-dependent, and research continues to delineate their biology.

Biological significance: tiRNAs are conserved across diverse eukaryotes and are implicated in the cellular response to stress, influencing cell survival, apoptosis, and adaptation. Abnormal tiRNA production has been linked to disease states such as cancer and neurodegenerative disorders in some studies, raising interest in their potential as biomarkers or therapeutic targets. Overall, tiRNAs represent a rapidly evolving area of RNA biology with ongoing efforts to define their full functional repertoire.