title: Minor introns are embedded molecular switches regulated by highly unstable U6atac snRNA.
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.
authors.affiliation: Department of Biochemistry and Biophysics , Howard Hughes Medical Institute, University of Pennsylvania School of Medicine , Philadelphia , United States.
authors.forename: Ihab
authors.initials: I
authors.lastname: Younis
authors.forename: Kimberly
authors.initials: K
authors.lastname: Dittmar
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Shawn W
authors.initials: SW
authors.lastname: Foley
authors.forename: Michael G
authors.initials: MG
authors.lastname: Berg
authors.forename: Karen Y
authors.initials: KY
authors.lastname: Hu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wei
authors.forename: Lili
authors.initials: L
authors.lastname: Wan
authors.forename: Gideon
authors.initials: G
authors.lastname: Dreyfuss
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D007438:Introns; D018384:Oxidative Stress; D012326:RNA Splicing; D012342:RNA, Small Nuclear / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017931:DNA Primers; D012342:RNA, Small Nuclear; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Human; U6atac; gene regulation; snRNA; splicing
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