Transcriptomics

Dataset Information

0

THUMPD2 catalyzes N2-methylation on the spliceosome catalytic center of U6 snRNA and regulates pre-mRNA splicing and retina degeneration


ABSTRACT: How the relatively evolutionarily conserved spliceosome is able to manage the enormously expanded number of splicing events that occur in humans (~200,000 vs. ~400 reported for yeast) is not well understood. Here, we show deposition of one RNA modification-N2-methylguanosine (m2G)-on the G72 nucleoside of U6 snRNA (known to function as the catalytic center of the spliceosome) results in profoundly increased pre-mRNA splicing activity in human cells. This U6 m2G72 modification is conserved among vertebrates. Further, we demonstrate that THUMPD2 is the methyltransferase responsible for U6 m2G72 and show that it interacts with an auxiliary protein (TRMT112) to specifically recognize both sequence and structural elements of U6. THUMPD2 KO blocks U6 m2G72 and down-regulates the pre-mRNA splicing activity of major spliceosome, yielding thousands of changed alternative splicing events of endogenous pre-mRNAs. Notably, the aberrantly spliced pre-mRNA population of the THUMPD2 KO cells elicits the nonsense-mediated mRNA decay (NMD) pathway and restricts cell proliferation. We also show that THUMPD2-mediated control of the U6 m2G72 modification is associated with age-related macular degeneration and retinal function. Our study thus demonstrates how an RNA epigenetic modification of the major spliceosome differentially regulates global mRNA splicing and impacts physiology and disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE236689 | GEO | 2024/01/02

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2023-05-17 | GSE219260 | GEO
2023-05-17 | PXD038967 | Pride
2023-05-17 | PXD038997 | Pride
2014-08-08 | E-GEOD-60195 | biostudies-arrayexpress
2014-08-08 | GSE60195 | GEO
| PRJNA992056 | ENA
2014-08-08 | E-GEOD-60197 | biostudies-arrayexpress
2014-08-08 | E-GEOD-60196 | biostudies-arrayexpress
2014-08-08 | GSE60196 | GEO
2014-08-08 | GSE60197 | GEO