5tiRNAs

5tiRNAs, or 5′ tRNA-derived stress-induced RNAs, are a class of small non-coding RNAs generated from the 5′ end of mature transfer RNAs (tRNAs). They are part of the broader family of tRNA-derived fragments (tRFs) and are distinguished from full-length tRNAs and from their 3′ counterparts.

Biogenesis and characteristics: Under cellular stress, ribonucleases such as angiogenin cleave mature tRNAs within the anticodon loop, producing 5′ and 3′ tRNA halves. The 5′tiRNA typically spans about 28–30 nucleotides, ending near the anticodon region. While angiogenin is the primary enzyme implicated in their production, other nucleases may contribute in certain contexts. 5′tiRNAs accumulate in the cytoplasm of stressed cells and can be detected by small RNA sequencing or Northern blotting.

Functions and roles: 5′tiRNAs are known to influence translation and stress responses. They can repress global protein synthesis by interfering with the assembly or function of the eIF4F cap-binding complex, thereby inhibiting initiation and promoting the formation of stress granules with RNA-binding proteins such as G3BP1. In addition to general translation control, 5′tiRNAs may participate in more selective regulatory processes and modulate RNA stability or signaling pathways during stress. The exact effects can vary depending on cell type and stress condition.

Context and relevance: 5tiRNAs are studied for their roles in cellular stress responses, with interest in how tRNA-derived fragments contribute to disease biology, including aging, cancer, and neurodegenerative conditions. They are distinguished from other tiRNA classes by their 5′ origin and characteristic size, and are typically investigated using small RNA sequencing and targeted assays.