Regulation of mRNA levels by decay-promoting introns that recruit the exosome specificity factor Mmi1
In eukaryotic cells, inefficient splicing is surprisingly common and leads to degradation of transcripts with retained introns. How pre-mRNAs are committed to nuclear decay is unknown. Here we uncover a mechanism by which specific intron-containing transcripts are targeted for nuclear degradation in...
| Những tác giả chính: | , , , , , |
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| Định dạng: | Journal article |
| Ngôn ngữ: | English |
| Được phát hành: |
Cell Press
2015
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| _version_ | 1826297662787289088 |
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| author | Kilchert, C Wittmann, S Passoni, M Shah, S Granneman, S Vasiljeva, L |
| author_facet | Kilchert, C Wittmann, S Passoni, M Shah, S Granneman, S Vasiljeva, L |
| author_sort | Kilchert, C |
| collection | OXFORD |
| description | In eukaryotic cells, inefficient splicing is surprisingly common and leads to degradation of transcripts with retained introns. How pre-mRNAs are committed to nuclear decay is unknown. Here we uncover a mechanism by which specific intron-containing transcripts are targeted for nuclear degradation in fission yeast. Sequence elements within these “decay-promoting” introns co-transcriptionally recruit the exosome specificity factor Mmi1, which induces degradation of the unspliced precursor and leads to a reduction of levels of the spliced mRNA. This mechanism negatively regulates levels of the RNA-helicase DDX5/Dbp2 to promote cell survival in response to stress. In contrast, fast removal of decay-promoting introns by co-transcriptional splicing precludes Mmi1 recruitment and relieves negative expression regulation. We propose that decay-promoting introns facilitate regulation of gene expression. Based on the identification of multiple additional Mmi1 targets including mRNAs, long non-coding RNAs, and sn/snoRNAs, we suggest a general role in RNA regulation for Mmi1 through transcript degradation. |
| first_indexed | 2024-03-07T04:35:05Z |
| format | Journal article |
| id | oxford-uuid:cfa83518-09c3-4cc8-9e06-2653ec7609a1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:35:05Z |
| publishDate | 2015 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:cfa83518-09c3-4cc8-9e06-2653ec7609a12022-03-27T07:44:14ZRegulation of mRNA levels by decay-promoting introns that recruit the exosome specificity factor Mmi1Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cfa83518-09c3-4cc8-9e06-2653ec7609a1EnglishSymplectic Elements at OxfordCell Press2015Kilchert, CWittmann, SPassoni, MShah, SGranneman, SVasiljeva, LIn eukaryotic cells, inefficient splicing is surprisingly common and leads to degradation of transcripts with retained introns. How pre-mRNAs are committed to nuclear decay is unknown. Here we uncover a mechanism by which specific intron-containing transcripts are targeted for nuclear degradation in fission yeast. Sequence elements within these “decay-promoting” introns co-transcriptionally recruit the exosome specificity factor Mmi1, which induces degradation of the unspliced precursor and leads to a reduction of levels of the spliced mRNA. This mechanism negatively regulates levels of the RNA-helicase DDX5/Dbp2 to promote cell survival in response to stress. In contrast, fast removal of decay-promoting introns by co-transcriptional splicing precludes Mmi1 recruitment and relieves negative expression regulation. We propose that decay-promoting introns facilitate regulation of gene expression. Based on the identification of multiple additional Mmi1 targets including mRNAs, long non-coding RNAs, and sn/snoRNAs, we suggest a general role in RNA regulation for Mmi1 through transcript degradation. |
| spellingShingle | Kilchert, C Wittmann, S Passoni, M Shah, S Granneman, S Vasiljeva, L Regulation of mRNA levels by decay-promoting introns that recruit the exosome specificity factor Mmi1 |
| title | Regulation of mRNA levels by decay-promoting introns that recruit the exosome specificity factor Mmi1 |
| title_full | Regulation of mRNA levels by decay-promoting introns that recruit the exosome specificity factor Mmi1 |
| title_fullStr | Regulation of mRNA levels by decay-promoting introns that recruit the exosome specificity factor Mmi1 |
| title_full_unstemmed | Regulation of mRNA levels by decay-promoting introns that recruit the exosome specificity factor Mmi1 |
| title_short | Regulation of mRNA levels by decay-promoting introns that recruit the exosome specificity factor Mmi1 |
| title_sort | regulation of mrna levels by decay promoting introns that recruit the exosome specificity factor mmi1 |
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