The making and breaking of tRNAs by ribonucleases.

Recent cryo-electron microscopy (cryo-EM) structures have offered critical new insights into the molecular mechanisms governing tRNA biogenesis. Structural and functional studies along with new advances in tRNA sequencing have revealed new details on the processing of tRNAs into tRNA-derived fragments (tRFs) by RNase A family members, RNase L, and Dicer. Recent structural advances and reconstitution experiments have provided new insights into the mechanism of surveillance and decay of tRNAs by exoribonucleases, including the Xrn nucleases and the exosome. Ribonucleases (RNases) such as the SLFN family, ANKZF1, and SAMD9 have new links with tRNA quality control and cellular defense mechanisms. Defining the cellular cues and molecular mechanisms that regulate tRNA processing and decay will enhance our understanding of human diseases associated with tRNA dysregulation. Ribonucleases (RNases) play important roles in supporting canonical and non-canonical roles of tRNAs by catalyzing the cleavage of the tRNA phosphodiester backbone. Here, we highlight how recent advances in cryo-electron microscopy (cryo-EM), protein structure prediction, reconstitution experiments, tRNA sequencing, and other studies have revealed new insight into the nucleases that process tRNA. This represents a very diverse group of nucleases that utilize distinct mechanisms to recognize and cleave tRNA during different stages of a tRNA's life cycle including biogenesis, fragmentation, surveillance, and decay. In this review, we provide a synthesis of the structure, mechanism, regulation, and modes of tRNA recognition by tRNA nucleases, along with open questions for future investigation. [ABSTRACT FROM AUTHOR]