Role of tRNA-Derived Fragments in Protozoan Parasite Biology

Highlights tsRNAs are small RNAs generated through specific cleavage of parent tRNAs, found across all domains of life, including protozoan parasites. tsRNAs are classified into tRNA halves formed by cleavage of a mature tRNA molecule at the anti-codon loop, or tRNA fragments, formed by cleavage of both pre- and mature- tRNAs at various positions. Various functions of tsRNAS have been identified including modulation of gene expression, translation inhibition, and response to cellular stress. tsRNAs have also been found to be packaged into extracellular vesicles and transported into host cells to modulate their gene expression. tRFs are formed by cleaving parent tRNA molecules into halves or smaller fragments.Abstract tRNA molecules are among the most fundamental and evolutionarily conserved RNA types, primarily facilitating the translation of genetic information from mRNA into proteins. Beyond their canonical role as adaptor molecules during protein synthesis, tRNAs have evolved to perform additional functions. One such non-canonical role for tRNAs is through the generation of tRNA-derived fragments via specific cleavage processes. These tRNA-derived small RNAs (tsRNAs) are present across all three domains of life, including in protozoan parasites. They are formed through the cleavage of the parent tRNA molecules at different sites, resulting in either tRNA halves or smaller fragments. The precise mechanisms underlying the synthesis of various tRNA-derived fragments, including the specific RNases involved, as well as their distinct functions and roles in parasite physiology, are not yet fully understood and remain an active area of ongoing research. However, their role in modulating gene expression, particularly during stress responses, is becoming increasingly evident. In this context, we discuss recent findings on the roles of tRNA-derived small RNA in various protozoan parasites. Furthermore, we investigate how these tsRNAs either modulate gene expression within the parasite itself or are packaged into extracellular vesicles to alter host gene expression, thereby promoting parasite survival and adaptation.