Transfer RNA-derived small RNAs: from biogenesis to regulatory roles in male reproductive system

With the advancement of next-generation sequencing technologies, transfer RNA (tRNA)-derived small RNAs (tsRNAs) have been progressively elucidated in their biogenesis and classification. tsRNAs are derived from precursor tRNAs (pre-tRNAs) or mature tRNAs and are classified into tRNA-derived fragments (tRFs) and tRNA-derived stress-induced RNAs (tiRNAs) based on their specific endonuclease cleavage sites and are functionally involved in diverse biological processes. tsRNAs are widely distributed within cells and are also present in the male reproductive system. Specifically, tRFs are the predominant tsRNA subspecies with established regulatory functions, whereas tiRNAs are less abundant and their roles remain less characterized. Notably, tsRNAs are particularly abundant in mature sperm, serving as vectors of paternal epigenetic inheritance. Multiple studies have shown that environmental factors and dietary modifications can significantly alter tsRNA profiles in the male reproductive system. Moreover, sperm tsRNAs regulate embryonic quality and are closely associated with male fertility. Collectively, these findings reveal the diverse roles of tsRNAs in male reproductive health and their potential as clinical biomarkers.