Abstract |
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. DOI:http://dx.doi.org/10.7554/eLife.00780.001.
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Authors | Ihab Younis, Kimberly Dittmar, Wei Wang, Shawn W Foley, Michael G Berg, Karen Y Hu, Zhi Wei, Lili Wan, Gideon Dreyfuss |
Journal | eLife
(Elife)
Vol. 2
Pg. e00780
(Jul 30 2013)
ISSN: 2050-084X [Print] England |
PMID | 23908766
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA Primers
- RNA, Small Nuclear
- p38 Mitogen-Activated Protein Kinases
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Topics |
- Base Sequence
- DNA Primers
- Enzyme Activation
- Gene Expression Regulation
- Introns
- Oxidative Stress
- RNA Splicing
- RNA, Small Nuclear
(physiology)
- Real-Time Polymerase Chain Reaction
- Up-Regulation
- p38 Mitogen-Activated Protein Kinases
(metabolism)
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