6DCC

Structure of methylphosphate capping enzyme methyltransferase domain in complex with 5' end of 7SK RNA

Summary for 6DCC

• Entry DOI: 10.2210/pdb6dcc/pdb
• Descriptor: 7SK snRNA methylphosphate capping enzyme, human 7SK RNA stem-loop 1 proximal methylated, S-ADENOSYL-L-HOMOCYSTEINE, ... (5 entities in total)
• Functional Keywords: rna methyl transferase, mepce, 7sk rna, transferase-rna complex, transferase/rna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 47327.12

Authors

Yang, Y.,Eichhorn, C.,Cascio, D.,Feigon, J. (deposition date: 2018-05-04, release date: 2018-12-19, Last modification date: 2023-10-11)

Primary citation

Yang, Y.,Eichhorn, C.D.,Wang, Y.,Cascio, D.,Feigon, J.
Structural basis of 7SK RNA 5'-gamma-phosphate methylation and retention by MePCE.
Nat. Chem. Biol., 15:132-140, 2019

PubMed Abstract: Among RNA 5'-cap structures, γ-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-Å 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.

PubMed: 30559425
DOI: 10.1038/s41589-018-0188-z

Experimental method

X-RAY DIFFRACTION (2.1 Å)