Structural highlights
Function
[MEPCE_HUMAN] S-adenosyl-L-methionine-dependent methyltransferase that adds a methylphosphate cap at the 5'-end of 7SK snRNA, leading to stabilize it.[1]
Publication Abstract from PubMed
Among RNA 5'-cap structures, gamma-phosphate monomethylation is unique to a small subset of noncoding RNAs, 7SK and U6 in humans. 7SK is capped by methylphosphate capping enzyme (MePCE), which has a second nonenzymatic role as a core component of the 7SK ribonuclear protein (RNP), an essential regulator of RNA transcription. We report 2.0- and 2.1-A X-ray crystal structures of the human MePCE methyltransferase domain bound to S-adenosylhomocysteine (SAH) and uncapped or capped 7SK substrates, respectively. 7SK recognition is achieved by protein contacts to a 5'-hairpin-single-stranded RNA region, thus explaining MePCE's specificity for 7SK and U6. The structures reveal SAH and product RNA in a near-transition-state geometry. Unexpectedly, binding experiments showed that MePCE has higher affinity for capped versus uncapped 7SK, and kinetic data support a model of slow product release. This work reveals the molecular mechanism of methyl transfer and 7SK retention by MePCE for subsequent assembly of 7SK RNP.
Structural basis of 7SK RNA 5'-gamma-phosphate methylation and retention by MePCE.,Yang Y, Eichhorn CD, Wang Y, Cascio D, Feigon J Nat Chem Biol. 2018 Dec 17. pii: 10.1038/s41589-018-0188-z. doi:, 10.1038/s41589-018-0188-z. PMID:30559425[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jeronimo C, Forget D, Bouchard A, Li Q, Chua G, Poitras C, Therien C, Bergeron D, Bourassa S, Greenblatt J, Chabot B, Poirier GG, Hughes TR, Blanchette M, Price DH, Coulombe B. Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme. Mol Cell. 2007 Jul 20;27(2):262-74. PMID:17643375 doi:http://dx.doi.org/10.1016/j.molcel.2007.06.027
- ↑ Yang Y, Eichhorn CD, Wang Y, Cascio D, Feigon J. Structural basis of 7SK RNA 5'-gamma-phosphate methylation and retention by MePCE. Nat Chem Biol. 2018 Dec 17. pii: 10.1038/s41589-018-0188-z. doi:, 10.1038/s41589-018-0188-z. PMID:30559425 doi:http://dx.doi.org/10.1038/s41589-018-0188-z
