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PDBsum entry 2mvs
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DOI no:
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J Am Chem Soc
137:2107-2115
(2015)
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PubMed id:
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Structure and thermodynamics of N6-methyladenosine in RNA: a spring-loaded base modification.
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C.Roost,
S.R.Lynch,
P.J.Batista,
K.Qu,
H.Y.Chang,
E.T.Kool.
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ABSTRACT
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N(6)-Methyladenosine (m(6)A) modification is hypothesized to control processes
such as RNA degradation, localization, and splicing. However, the molecular
mechanisms by which this occurs are unclear. Here, we measured structures of an
RNA duplex containing m(6)A in the GGACU consensus, along with an unmodified RNA
control, by 2D NMR. The data show that m(6)A-U pairing in the double-stranded
context is accompanied by the methylamino group rotating from its energetically
preferred syn geometry on the Watson-Crick face to the higher-energy anti
conformation, positioning the methyl group in the major groove. Thermodynamic
measurements of m(6)A in duplexes reveal that it is destabilizing by 0.5-1.7
kcal/mol. In contrast, we show that m(6)A in unpaired positions base stacks
considerably more strongly than the unmodified base, adding substantial
stabilization in single-stranded locations. Transcriptome-wide nuclease mapping
of methylated RNA secondary structure from human cells reveals a structural
transition at methylated adenosines, with a tendency to single-stranded
structure adjacent to the modified base.
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');
}
}
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