Ihab Younis, Kimberly Dittmar, Wei Wang, Shawn W Foley, Michael G Berg, Karen Y Hu, Zhi Wei, Lili Wan, Gideon Dreyfuss
eLife 2013 Jul 30Eukaryotes 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.
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. 2013 Jul 30;2:e00780
PMID: 23908766
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