SF3B1 association with chromatin determines splicing outcomes
Much remains unknown concerning the mechanism by which the splicing machinery pinpoints short exons within intronic sequences and how splicing factors are directed to their pre-mRNA targets. One probable explanation lies in differences in chromatin organization between exons and introns. Proteomic,...
| Main Authors: | , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2015
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/107367 http://hdl.handle.net/10220/25580 |
| _version_ | 1826117808357900288 |
|---|---|
| author | Kfir, Nir Lev-Maor, Galit Glaich, Ohad Alajem, Adi Datta, Arnab Sze, Siu K. Meshorer, Eran Ast, Gil |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Kfir, Nir Lev-Maor, Galit Glaich, Ohad Alajem, Adi Datta, Arnab Sze, Siu K. Meshorer, Eran Ast, Gil |
| author_sort | Kfir, Nir |
| collection | NTU |
| description | Much remains unknown concerning the mechanism by which the splicing machinery pinpoints short exons within intronic sequences and how splicing factors are directed to their pre-mRNA targets. One probable explanation lies in differences in chromatin organization between exons and introns. Proteomic, co-immunoprecipitation, and sedimentation analyses described here indicate that SF3B1, an essential splicing component of the U2 snRNP complex, is strongly associated with nucleosomes. ChIP-seq and RNA-seq analyses reveal that SF3B1 specifically binds nucleosomes located at exonic positions. SF3B1 binding is enriched at nucleosomes positioned over short exons flanked by long introns that are also characterized by differential GC contentbetween exons and introns. Disruption of SF3B1 binding to such nucleosomes affects splicing of these exons similarly to SF3B1 knockdown. Ourfindings suggest that the association of SF3B1 with nucleosomes is functionally important for splice-site recognition and that SF3B1 conveys splicing-relevant information embedded in chromatin structure. |
| first_indexed | 2024-10-01T04:33:24Z |
| format | Journal Article |
| id | ntu-10356/107367 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:33:24Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | ntu-10356/1073672023-02-28T17:06:27Z SF3B1 association with chromatin determines splicing outcomes Kfir, Nir Lev-Maor, Galit Glaich, Ohad Alajem, Adi Datta, Arnab Sze, Siu K. Meshorer, Eran Ast, Gil School of Biological Sciences DRNTU::Science::Biological sciences Much remains unknown concerning the mechanism by which the splicing machinery pinpoints short exons within intronic sequences and how splicing factors are directed to their pre-mRNA targets. One probable explanation lies in differences in chromatin organization between exons and introns. Proteomic, co-immunoprecipitation, and sedimentation analyses described here indicate that SF3B1, an essential splicing component of the U2 snRNP complex, is strongly associated with nucleosomes. ChIP-seq and RNA-seq analyses reveal that SF3B1 specifically binds nucleosomes located at exonic positions. SF3B1 binding is enriched at nucleosomes positioned over short exons flanked by long introns that are also characterized by differential GC contentbetween exons and introns. Disruption of SF3B1 binding to such nucleosomes affects splicing of these exons similarly to SF3B1 knockdown. Ourfindings suggest that the association of SF3B1 with nucleosomes is functionally important for splice-site recognition and that SF3B1 conveys splicing-relevant information embedded in chromatin structure. Published version 2015-05-18T06:55:28Z 2019-12-06T22:29:23Z 2015-05-18T06:55:28Z 2019-12-06T22:29:23Z 2015 2015 Journal Article Kfir, N., Lev-Maor, G., Glaich, O., Alajem, A., Datta, A., Sze, S., et al. (2015). SF3B1 association with chromatin determines splicing outcomes. Cell reports, 11(4), 618-629. 2211-1247 https://hdl.handle.net/10356/107367 http://hdl.handle.net/10220/25580 10.1016/j.celrep.2015.03.048 en Cell reports © 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences Kfir, Nir Lev-Maor, Galit Glaich, Ohad Alajem, Adi Datta, Arnab Sze, Siu K. Meshorer, Eran Ast, Gil SF3B1 association with chromatin determines splicing outcomes |
| title | SF3B1 association with chromatin determines splicing outcomes |
| title_full | SF3B1 association with chromatin determines splicing outcomes |
| title_fullStr | SF3B1 association with chromatin determines splicing outcomes |
| title_full_unstemmed | SF3B1 association with chromatin determines splicing outcomes |
| title_short | SF3B1 association with chromatin determines splicing outcomes |
| title_sort | sf3b1 association with chromatin determines splicing outcomes |
| topic | DRNTU::Science::Biological sciences |
| url | https://hdl.handle.net/10356/107367 http://hdl.handle.net/10220/25580 |
| work_keys_str_mv | AT kfirnir sf3b1associationwithchromatindeterminessplicingoutcomes AT levmaorgalit sf3b1associationwithchromatindeterminessplicingoutcomes AT glaichohad sf3b1associationwithchromatindeterminessplicingoutcomes AT alajemadi sf3b1associationwithchromatindeterminessplicingoutcomes AT dattaarnab sf3b1associationwithchromatindeterminessplicingoutcomes AT szesiuk sf3b1associationwithchromatindeterminessplicingoutcomes AT meshorereran sf3b1associationwithchromatindeterminessplicingoutcomes AT astgil sf3b1associationwithchromatindeterminessplicingoutcomes |