Minor introns are embedded molecular switches regulated by highly unstable U6atac snRNA
Eukaryotes have two types of spliceosomes, comprised of either major (U1, U2, U4, U5, U6) or minor (U11, U12, U4atac, U6atac; <1%) snRNPs. The high conservation of minor introns, typically one amidst many major introns in several hundred genes, despite their poor splicing, has been a long-sta...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2013-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/00780 |
| _version_ | 1811199629352501248 |
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| author | Ihab Younis Kimberly Dittmar Wei Wang Shawn W Foley Michael G Berg Karen Y Hu Zhi Wei Lili Wan Gideon Dreyfuss |
| author_facet | Ihab Younis Kimberly Dittmar Wei Wang Shawn W Foley Michael G Berg Karen Y Hu Zhi Wei Lili Wan Gideon Dreyfuss |
| author_sort | Ihab Younis |
| collection | DOAJ |
| description | Eukaryotes have two types of spliceosomes, comprised of either major (U1, U2, U4, U5, U6) or minor (U11, U12, U4atac, U6atac; <1%) snRNPs. The high conservation of minor introns, typically one amidst many major introns in several hundred genes, despite their poor splicing, has been a long-standing enigma. Here, we discovered that the low abundance minor spliceosome’s catalytic snRNP, U6atac, is strikingly unstable (t½<2 hr). We show that U6atac level depends on both RNA polymerases II and III and can be rapidly increased by cell stress-activated kinase p38MAPK, which stabilizes it, enhancing mRNA expression of hundreds of minor intron-containing genes that are otherwise suppressed by limiting U6atac. Furthermore, p38MAPK-dependent U6atac modulation can control minor intron-containing tumor suppressor PTEN expression and cytokine production. We propose that minor introns are embedded molecular switches regulated by U6atac abundance, providing a novel post-transcriptional gene expression mechanism and a rationale for the minor spliceosome’s evolutionary conservation. |
| first_indexed | 2024-04-12T01:50:35Z |
| format | Article |
| id | doaj.art-880ce9671c444546922cf4312c02e818 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:50:35Z |
| publishDate | 2013-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-880ce9671c444546922cf4312c02e8182022-12-22T03:52:57ZengeLife Sciences Publications LtdeLife2050-084X2013-07-01210.7554/eLife.00780Minor introns are embedded molecular switches regulated by highly unstable U6atac snRNAIhab Younis0Kimberly Dittmar1Wei Wang2Shawn W Foley3Michael G Berg4Karen Y Hu5Zhi Wei6Lili Wan7Gideon Dreyfuss8Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, United StatesDepartment of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, United StatesDepartment of Computer Science, New Jersey Institute of Technology, Newark, United StatesDepartment of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, United StatesDepartment of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, United StatesDepartment of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, United StatesDepartment of Computer Science, New Jersey Institute of Technology, Newark, United StatesDepartment of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, United StatesDepartment of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, United StatesEukaryotes have two types of spliceosomes, comprised of either major (U1, U2, U4, U5, U6) or minor (U11, U12, U4atac, U6atac; <1%) snRNPs. The high conservation of minor introns, typically one amidst many major introns in several hundred genes, despite their poor splicing, has been a long-standing enigma. Here, we discovered that the low abundance minor spliceosome’s catalytic snRNP, U6atac, is strikingly unstable (t½<2 hr). We show that U6atac level depends on both RNA polymerases II and III and can be rapidly increased by cell stress-activated kinase p38MAPK, which stabilizes it, enhancing mRNA expression of hundreds of minor intron-containing genes that are otherwise suppressed by limiting U6atac. Furthermore, p38MAPK-dependent U6atac modulation can control minor intron-containing tumor suppressor PTEN expression and cytokine production. We propose that minor introns are embedded molecular switches regulated by U6atac abundance, providing a novel post-transcriptional gene expression mechanism and a rationale for the minor spliceosome’s evolutionary conservation.https://elifesciences.org/articles/00780snRNAU6atacsplicinggene regulation |
| spellingShingle | Ihab Younis Kimberly Dittmar Wei Wang Shawn W Foley Michael G Berg Karen Y Hu Zhi Wei Lili Wan Gideon Dreyfuss Minor introns are embedded molecular switches regulated by highly unstable U6atac snRNA eLife snRNA U6atac splicing gene regulation |
| title | Minor introns are embedded molecular switches regulated by highly unstable U6atac snRNA |
| title_full | Minor introns are embedded molecular switches regulated by highly unstable U6atac snRNA |
| title_fullStr | Minor introns are embedded molecular switches regulated by highly unstable U6atac snRNA |
| title_full_unstemmed | Minor introns are embedded molecular switches regulated by highly unstable U6atac snRNA |
| title_short | Minor introns are embedded molecular switches regulated by highly unstable U6atac snRNA |
| title_sort | minor introns are embedded molecular switches regulated by highly unstable u6atac snrna |
| topic | snRNA U6atac splicing gene regulation |
| url | https://elifesciences.org/articles/00780 |
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