Year: 2012
Type: article
Abstract: Eukaryotic gene expression involves tight coordination between transcription and pre-mRNA splicing; however, factors responsible for this coordination remain incompletely defined. Here, we explored the genetic, functional, and biochemical interactions of a likely coordinator, Npl3, an SR-like protein in Saccharomyces cerevisiae that we recently showed is required for efficient co-transcriptional recruitment of the splicing machinery. We surveyed the NPL3 genetic interaction space and observed a significant enrichment for genes involved in histone modification and chromatin remodeling. Specifically, we found that Npl3 genetically interacts with both Bre1, which mono-ubiquitinates histone H2B as part of the RAD6 Complex, and Ubp8, the de-ubiquitinase of the SAGA Complex. In support of these genetic data, we show that Bre1 physically interacts with Npl3 in an RNA-independent manner. Furthermore, using a genome-wide splicing microarray, we found that the known splicing defect of a strain lacking Npl3 is exacerbated by deletion of BRE1 or UBP8, a phenomenon phenocopied by a point mutation in H2B that abrogates ubiquitination. Intriguingly, even in the presence of wild-type NPL3, deletion of BRE1 exhibits a mild splicing defect and elicits a growth defect in combination with deletions of early and late splicing factors. Taken together, our data reveal a connection between Npl3 and an extensive array of chromatin factors and describe an unanticipated functional link between histone H2B ubiquitination and pre-mRNA splicing.
Source: PLoS Genetics
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Funders: National Science Foundation, American Cancer Society, Irish Research Council for Science, Engineering and Technology, Science Foundation Ireland, National Institutes of Health, U.S. Public Health Service, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Awards: Genetic Analysis of the Nucleosome and RNA Polymerase II: A Systems Approach, SRC Clique: Graph & Network Analysis Cluster, Exploring Design Principles of Cellular Control Circuits, G2528919290, G3380533055, Comparative Analysis of Genetic Interaction Networks, G5951746209, G6276702551, G9000218453, UCSF-Bay Area Center for AIDS Research
OpenAlex ID: W2069258716