You are here

Minor introns are embedded molecular switches regulated by highly unstable U6atac snRNA

Authors: 
Younis I, Dittmar K, Wang W, Foley SW, Berg MG, Hu KY, Wei Z, Wan L, Dreyfuss G
Citation: 
eLife. 2013;doi:10.7554/eLife.00780
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.
Organism or Cell Type: 
cell culture: HeLa cells
Delivery Method: 
Electroporatoin (Neon, Life Technologies)