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PDBsum entry 6dcc
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Transferase/RNA
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PDB id
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6dcc
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References listed in PDB file
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Key reference
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Title
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Structural basis of 7sk RNA 5'-γ-Phosphate methylation and retention by mepce.
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Authors
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Y.Yang,
C.D.Eichhorn,
Y.Wang,
D.Cascio,
J.Feigon.
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Ref.
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Nat Chem Biol, 2019,
15,
132-140.
[DOI no: ]
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PubMed id
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Abstract
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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.
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