7p3b

Publication Abstract from PubMed

RtcB enzymes are RNA ligases that play essential roles in tRNA splicing, unfolded protein response, and RNA repair. In metazoa, RtcB functions as part of a five-subunit tRNA ligase complex (tRNA-LC) along with Ddx1, Cgi-99, Fam98B, and Ashwin. The human tRNA-LC or its individual subunits have been implicated in additional cellular processes including microRNA maturation, viral replication, DNA double-strand break repair, and mRNA transport. Here, we present a biochemical analysis of the inter-subunit interactions within the human tRNA-LC along with crystal structures of the catalytic subunit RTCB and the N-terminal domain of CGI-99. We show that the core of the human tRNA-LC is assembled from RTCB and the C-terminal alpha-helical regions of DDX1, CGI-99, and FAM98B, all of which are required for complex integrity. The N-terminal domain of CGI-99 displays structural homology to calponin-homology domains, and CGI-99 and FAM98B associate via their N-terminal domains to form a stable subcomplex. The crystal structure of GMP-bound RTCB reveals divalent metal coordination geometry in the active site, providing insights into its catalytic mechanism. Collectively, these findings shed light on the molecular architecture and mechanism of the human tRNA ligase complex and provide a structural framework for understanding its functions in cellular RNA metabolism.

Molecular architecture of the human tRNA ligase complex.,Kroupova A, Ackle F, Asanovic I, Weitzer S, Boneberg FM, Faini M, Leitner A, Chui A, Aebersold R, Martinez J, Jinek M Elife. 2021 Dec 2;10. pii: 71656. doi: 10.7554/eLife.71656. PMID:34854379^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.