| Structural highlights
Function
GRC3_YEAST Polynucleotide 5'-kinase involved in rRNA processing. Required for the efficient termination by RNA polymerase I and the processing of the IST2 pre-rRNA internal transcribed spacer localized between the 5.8S and 25S rRNAs. May act by maintaining the phosphorylated status of the downstream RNT1 cleavage product, which in turn allows the torpedo activity of RAT1 to efficiently terminate Pol I transcription. In vitro, displays polynucleotide kinase activity on both single- and double-stranded RNA and on single-stranded DNA alone, but not double-stranded DNA alone.[1] [2]
Publication Abstract from PubMed
Precursor ribosomal RNA (pre-rRNA) processing is a key step in ribosome biosynthesis and involves numerous RNases. A HEPN (higher eukaryote and prokaryote nucleotide binding) nuclease Las1 and a polynucleotide kinase Grc3 assemble into a tetramerase responsible for rRNA maturation. Here, we report the structures of full-length Saccharomyces cerevisiae and Cyberlindnera jadinii Las1-Grc3 complexes, and C. jadinii Las1. The Las1-Grc3 structures show that the central coiled-coil domain of Las1 facilitates pre-rRNA binding and cleavage, while the Grc3 C-terminal loop motif directly binds to the HEPN active center of Las1 and regulates pre-rRNA cleavage. Structural comparison between Las1 and Las1-Grc3 complex exhibits that Grc3 binding induces conformational rearrangements of catalytic residues associated with HEPN nuclease activation. Biochemical assays identify that Las1 processes pre-rRNA at the two specific sites (C2 and C2'), which greatly facilitates rRNA maturation. Our structures and specific pre-rRNA cleavage findings provide crucial insights into the mechanism and pathway of pre-rRNA processing in ribosome biosynthesis.
Structural and mechanistic insights into ribosomal ITS2 RNA processing by nuclease-kinase machinery.,Chen J, Chen H, Li S, Lin X, Hu R, Zhang K, Liu L Elife. 2024 Jan 5;12:RP86847. doi: 10.7554/eLife.86847. PMID:38180340[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Peng WT, Robinson MD, Mnaimneh S, Krogan NJ, Cagney G, Morris Q, Davierwala AP, Grigull J, Yang X, Zhang W, Mitsakakis N, Ryan OW, Datta N, Jojic V, Pal C, Canadien V, Richards D, Beattie B, Wu LF, Altschuler SJ, Roweis S, Frey BJ, Emili A, Greenblatt JF, Hughes TR. A panoramic view of yeast noncoding RNA processing. Cell. 2003 Jun 27;113(7):919-33. PMID:12837249
- ↑ Braglia P, Heindl K, Schleiffer A, Martinez J, Proudfoot NJ. Role of the RNA/DNA kinase Grc3 in transcription termination by RNA polymerase I. EMBO Rep. 2010 Oct;11(10):758-64. PMID:20814424 doi:10.1038/embor.2010.130
- ↑ Chen J, Chen H, Li S, Lin X, Hu R, Zhang K, Liu L. Structural and mechanistic insights into ribosomal ITS2 RNA processing by nuclease-kinase machinery. Elife. 2024 Jan 5;12:RP86847. PMID:38180340 doi:10.7554/eLife.86847
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