Cassandra K Hayne, Casey A Schmidt, Maira I Haque, A Gregory Matera, and Robin E Stanley
Nucleic Acids Res (2020) 48 (14): 7609–7622. doi:10.1093/nar/gkaa438
This study describes the biochemical reconstitution and characterization of the human tRNA Splicing Endonuclease (‘TSEN’) complex. This work is a major step forward in elucidating roles of the individual components of the TSEN machinery. It demonstrates that the complex is active in the presence and absence of the CLP1 kinase and confirms the identity of critical residues in the active sites of the endonuclease subunits, showing that the mechanism of tRNA cleavage is well conserved across archaeal and eukaryotic homologues. It further reveals that CLP1 is not required for TSEN mediated tRNA intron removal in vivo. Instead CLP1 functions as a negative regulator of tRNA exon ligation and intron circularization, providing insight into the role that CLP1 plays in tRNA splicing.