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Peer-reviewedCC BY 4.0G3: Genes, Genomes, Genetics

S. cerevisiae Cwc15p tunes the spliceosome active site for remodeling and catalysis

  • Natalie J Zeps1
  • Giovanni Balice1
  • Elizabeth C Baudhuin1
  • Zach Freedman1
  • Sierra Jones2
  • Dennis Halterman2,3
  • Aaron A Hoskins1,4
4 affiliations
  1. 1Department of Biochemistry, University of Wisconsin-Madison , Madison, WI 53706 ,
  2. 2Department of Plant Pathology, University of Wisconsin-Madison , Madison, WI 53706 ,
  3. 3USDA-ARS Vegetable Crops Research Unit , Madison, WI 53706 ,
  4. 4Department of Chemistry, University of Wisconsin-Madison , Madison, WI 53706 ,
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Abstract

Pre-mRNA splicing is an essential step in eukaryotic gene expression during which spliceosomes remove introns from nascent RNAs while ligating the adjacent exons. Spliceosomes are cellular nanomachines composed of five small nuclear (snRNA) components and dozens of proteins, most of which are highly conserved. Despite the high conservation of many splicing factors between S. cerevisiae and H. sapiens, several protein components of the S. cerevisiae spliceosome are not essential for growth under normal laboratory conditions. This is particularly surprising for nonessential factors whose conserved domains contact the spliceosome's catalytic core. Uncovering a function for these splicing factors can be challenging since they are not required for viability, may engage in functionally redundant interactions, and may display only weak phenotypes in the absence of secondary mutations in other spliceosome components. One such nonessential factor is the Cwc15 protein. Cwc15's highly conserved N-terminus directly contacts the U2/U6 di-snRNA within the spliceosome catalytic core; yet its precise role in splicing has not been defined in any organism. In this work, we use molecular genetics in S. cerevisiae combined with splicing reporter assays to study Cwc15p function. We propose that Cwc15p not only promotes the stability of the active site but also its structural transitions. These functions may be critical for splicing in S. cerevisiae under nonoptimal conditions, facilitating use of weak or alternate splice sites, and could have implications for proofreading of spliceosome active site formation.

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Cite

BibTeXRIS
BibTeX
@article{zeps2026cerevisiae,
  title = {{S. cerevisiae Cwc15p tunes the spliceosome active site for remodeling and catalysis}},
  author = {Natalie J Zeps and Giovanni Balice and Elizabeth C Baudhuin and Zach Freedman and Sierra Jones and Dennis Halterman and Aaron A Hoskins},
  journal = {G3: Genes, Genomes, Genetics},
  year = {2026},
  month = oct,
  doi = {10.1093/g3journal/jkag280},
  url = {https://academic.oup.com/g3journal/advance-article/doi/10.1093/g3journal/jkag280/8860202},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - S. cerevisiae Cwc15p tunes the spliceosome active site for remodeling and catalysis
AU  - Natalie J Zeps
AU  - Giovanni Balice
AU  - Elizabeth C Baudhuin
AU  - Zach Freedman
AU  - Sierra Jones
AU  - Dennis Halterman
AU  - Aaron A Hoskins
PY  - 2026
DA  - 2026/10/03
JO  - G3: Genes, Genomes, Genetics
DO  - 10.1093/g3journal/jkag280
UR  - https://academic.oup.com/g3journal/advance-article/doi/10.1093/g3journal/jkag280/8860202
AB  - Pre-mRNA splicing is an essential step in eukaryotic gene expression during which spliceosomes remove introns from nascent RNAs while ligating the adjacent exons. Spliceosomes are cellular nanomachines composed of five small nuclear (snRNA) components and dozens of proteins, most of which are highly conserved. Despite the high conservation of many splicing factors between S. cerevisiae and H. sapiens, several protein components of the S. cerevisiae spliceosome are not essential for growth under normal laboratory conditions. This is particularly surprising for nonessential factors whose conserved domains contact the spliceosome's catalytic core. Uncovering a function for these splicing factors can be challenging since they are not required for viability, may engage in functionally redundant interactions, and may display only weak phenotypes in the absence of secondary mutations in other spliceosome components. One such nonessential factor is the Cwc15 protein. Cwc15's highly conserved N-terminus directly contacts the U2/U6 di-snRNA within the spliceosome catalytic core; yet its precise role in splicing has not been defined in any organism. In this work, we use molecular genetics in S. cerevisiae combined with splicing reporter assays to study Cwc15p function. We propose that Cwc15p not only promotes the stability of the active site but also its structural transitions. These functions may be critical for splicing in S. cerevisiae under nonoptimal conditions, facilitating use of weak or alternate splice sites, and could have implications for proofreading of spliceosome active site formation.
SN  - 2160-1836
ER  -