The yeast SR-like protein Npl3 links chromatin modification to mRNA processing.
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 protei...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3510044?pdf=render |
| _version_ | 1818503275750621184 |
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| author | Erica A Moehle Colm J Ryan Nevan J Krogan Tracy L Kress Christine Guthrie |
| author_facet | Erica A Moehle Colm J Ryan Nevan J Krogan Tracy L Kress Christine Guthrie |
| author_sort | Erica A Moehle |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T21:21:53Z |
| format | Article |
| id | doaj.art-34f69ade9b0244978aebc3c53f969912 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-10T21:21:53Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-34f69ade9b0244978aebc3c53f9699122022-12-22T01:33:06ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042012-01-01811e100310110.1371/journal.pgen.1003101The yeast SR-like protein Npl3 links chromatin modification to mRNA processing.Erica A MoehleColm J RyanNevan J KroganTracy L KressChristine GuthrieEukaryotic 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.http://europepmc.org/articles/PMC3510044?pdf=render |
| spellingShingle | Erica A Moehle Colm J Ryan Nevan J Krogan Tracy L Kress Christine Guthrie The yeast SR-like protein Npl3 links chromatin modification to mRNA processing. PLoS Genetics |
| title | The yeast SR-like protein Npl3 links chromatin modification to mRNA processing. |
| title_full | The yeast SR-like protein Npl3 links chromatin modification to mRNA processing. |
| title_fullStr | The yeast SR-like protein Npl3 links chromatin modification to mRNA processing. |
| title_full_unstemmed | The yeast SR-like protein Npl3 links chromatin modification to mRNA processing. |
| title_short | The yeast SR-like protein Npl3 links chromatin modification to mRNA processing. |
| title_sort | yeast sr like protein npl3 links chromatin modification to mrna processing |
| url | http://europepmc.org/articles/PMC3510044?pdf=render |
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