tRNAs and tRNA fragments as modulators of cardiac and skeletal muscle function

Transfer RNAs (tRNAs) and their processing enzymes have long-recognized roles in cardiac and skeletal muscle pathophysiology. Recently, tRNA fragments have emerged as a new class of non-coding RNAs involved in the regulation of cell function. In this review, we provide a synopsis of the molecular processes that regulate the biogenesis, post-transcriptional regulation and functional roles of tRNAs in cardiac and skeletal muscle. In addition, we list the (dys)regulated expression profiles and putative functional roles of tRNA-derived small RNAs in the heart and skeletal muscle. Finally, the technical challenges surrounding tRNA research are discussed alongside suggestions to advance research in this field. •tRFs are novel small regulatory RNAs with yet largely unknown functions.•tRFs are formed by specific enzymes, including Dicer and Angiogenin.•tRFs are present in diverse mammalian cell types and in the circulation.•tRNA transcription increases and tRF levels change upon cardiac pressure overload.•Knowledge on tRFs in the healthy and failing heart is still limited.