TY - JOUR
T1 - Minor introns are embedded molecular switches regulated by highly unstable U6atac snRNA
AU - Younis, Ihab
AU - Dittmar, Kimberly
AU - Wang, Wei
AU - Foley, Shawn W.
AU - Berg, Michael G.
AU - Hu, Karen Y.
AU - Wei, Zhi
AU - Wan, Lili
AU - Dreyfuss, Gideon
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/7/30
Y1 - 2013/7/30
N2 - 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 (t1/2<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.
AB - 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 (t1/2<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.
UR - http://www.scopus.com/inward/record.url?scp=84881083550&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84881083550&partnerID=8YFLogxK
U2 - 10.7554/eLife.00780
DO - 10.7554/eLife.00780
M3 - Article
C2 - 23908766
AN - SCOPUS:84881083550
SN - 2050-084X
VL - 2013
JO - eLife
JF - eLife
IS - 2
M1 - e00780
ER -