Transfer RNA Fragments, from Structure to Function

Transfer RNA molecules (tRNAs) are produced from numerous nuclear and mitochondrial genes and are primarily involved in bringing specific amino acid residues to polyribosomes and enabling correct elongation of polypeptide chains. Several different nucleases may degrade tRNA molecules into shorter oligonucleotide chains designated transfer RNA fragments (tRFs). It has recently been realized that these tRFs may resume diverse functions, including but not limited to enabling ribosomal activities, sperm cell differentiation, and interaction with messenger RNA transcripts (mRNA) carrying complementary sequence motifs. Such interaction can suppress the translation of those mRNAs and induce their degradation in a similar manner to that of microRNAs (miRs). Additionally, tRFs can interact with RNA-binding proteins and modulate translation processes and the functioning of transcription factors. This, in turn, can accelerate the division of some blood cell types, for example, in patients recovering from ischemic stroke. However, the full scope of tRFs structure–function relationships awaits further studies, addressing the specific conditions, cell types, tissues and organisms where tRFs are produced and function, as well as the dependence of their production on age, sex, health and disease. The rapidly accumulating knowledge about tRFs calls for approaching these issues and making the structure–function interrelationships of these intriguing molecules amenable for further exploration.