%0 Journal Article
%T Structural basis of 7SK RNA 5¡ä-¦Ã-phosphate methylation and retention by MePCE
%J -
%D 2018
%R https://doi.org/10.1038/s41589-018-0188-z
%X Among RNA 5¡ä-cap structures, ¦Ã-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-£¿ 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¡ä-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
%U https://www.nature.com/articles/s41589-018-0188-z