Structural highlights
Function
RTCB_HUMAN Catalytic subunit of the tRNA-splicing ligase complex that acts by directly joining spliced tRNA halves to mature-sized tRNAs by incorporating the precursor-derived splice junction phosphate into the mature tRNA as a canonical 3',5'-phosphodiester. May act as an RNA ligase with broad substrate specificity, and may function toward other RNAs.[HAMAP-Rule:MF_03144][1] [2]
Publication Abstract from PubMed
RNA ligases of the RTCB-type play an essential role in tRNA splicing, the unfolded protein response and RNA repair. RTCB is the catalytic subunit of the pentameric human tRNA ligase complex. RNA ligation by the tRNA ligase complex requires GTP-dependent activation of RTCB. This active site guanylylation reaction relies on the activation factor Archease. The mechanistic interplay between both proteins has remained unknown. Here, we report a biochemical and structural analysis of the human RTCB-Archease complex in the pre- and post-activation state. Archease reaches into the active site of RTCB and promotes the formation of a covalent RTCB-GMP intermediate through coordination of GTP and metal ions. During the activation reaction, Archease prevents futile RNA substrate binding to RTCB. Moreover, monomer structures of Archease and RTCB reveal additional states within the RNA ligation mechanism. Taken together, we present structural snapshots along the reaction cycle of the human tRNA ligase.
Structural and mechanistic insights into activation of the human RNA ligase RTCB by Archease.,Gerber JL, Morales Guzman SI, Worf L, Hubbe P, Kopp J, Peschek J Nat Commun. 2024 Mar 16;15(1):2378. doi: 10.1038/s41467-024-46568-2. PMID:38493148[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Popow J, Englert M, Weitzer S, Schleiffer A, Mierzwa B, Mechtler K, Trowitzsch S, Will CL, Lührmann R, Söll D, Martinez J. HSPC117 is the essential subunit of a human tRNA splicing ligase complex. Science. 2011 Feb 11;331(6018):760-4. PMID:21311021 doi:10.1126/science.1197847
- ↑ Popow J, Jurkin J, Schleiffer A, Martinez J. Analysis of orthologous groups reveals archease and DDX1 as tRNA splicing factors. Nature. 2014 Jul 3;511(7507):104-7. PMID:24870230 doi:10.1038/nature13284
- ↑ Gerber JL, Morales Guzmán SI, Worf L, Hubbe P, Kopp J, Peschek J. Structural and mechanistic insights into activation of the human RNA ligase RTCB by Archease. Nat Commun. 2024 Mar 16;15(1):2378. PMID:38493148 doi:10.1038/s41467-024-46568-2
