Cwc23 is a component of the NTR complex and functions to stabilize Ntr1 and facilitate disassembly of spliceosome intermediates

Abstract Cwc23 is a member of the J protein family, and has been shown to interact with Ntr1, a scaffold protein that interacts with Ntr2 and Prp43 to form the NTR complex that mediates spliceosome disassembly. We show that Cwc23 is also an intrinsic component of the NTR complex, and that it interac...

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Bibliographic Details
Published in:Nucleic acids research 2018-04, Vol.46 (7), p.3764-3773
Main Authors: Su, Yu-Lun, Chen, Hsin-Chou, Tsai, Rong-Tzong, Lin, Pei-Chun, Cheng, Soo-Chen
Format: Article
Language:English
Subjects:
Adenosine Triphosphatases - genetics
DEAD-box RNA Helicases - genetics
Introns - genetics
Molecular Chaperones - antagonists & inhibitors
Molecular Chaperones - genetics
Protein Binding
RNA and RNA-protein complexes
RNA Helicases - genetics
RNA Splicing - genetics
RNA Splicing Factors - genetics
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae Proteins - antagonists & inhibitors
Saccharomyces cerevisiae Proteins - genetics
Spliceosomes - genetics
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Summary:Abstract Cwc23 is a member of the J protein family, and has been shown to interact with Ntr1, a scaffold protein that interacts with Ntr2 and Prp43 to form the NTR complex that mediates spliceosome disassembly. We show that Cwc23 is also an intrinsic component of the NTR complex, and that it interacts with the carboxyl terminus of Ntr1. Metabolic depletion of Cwc23 concurrently depleted Ntr1 and Ntr2, suggesting a role for Cwc23 in stabilizing these two proteins. Ntr1, Ntr2 and Cwc23 are stoichiometrically balanced, and form a stable heterotrimer. Depletion of Cwc23 from splicing extracts using antibodies resulted in depletion of all three proteins and accumulation of intron-lariat in the splicing reaction. Cwc23 is not required for disassembly of intron-lariat spliceosome (ILS), but facilitates disassembly of spliceosome intermediates after the actions of Prp2 and Prp16 by stabilizing the association of Ntr1 with the spliceosome. Cwc23 has a more limited effect on the association of Ntr1 with the ILS. Our data suggest that Cwc23 is important for maintaining the levels of Ntr1 and Ntr2, and that it also plays a regulatory role in targeting spliceosome intermediates for disassembly.
ISSN:0305-1048
1362-4962
1362-4962
DOI:10.1093/nar/gky052