Effect of methylation of adenine N6 on kink turn structure depends on location

Saira Ashraf, Lin Huang, David Lilley (Lead / Corresponding author)

Research output: Contribution to journalArticle

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Abstract

N6-methyladenine is the most common covalent modification in cellular RNA species, with demonstrated functional consequences. At the molecular level this methylation could alter local RNA structure, and/or modulate the binding of specific proteins. We have previously shown that trans-Hoogsteen-sugar (sheared) A:G base pairs can be completely disrupted by methylation, and that this occurs in a sub-set of human box C/D k-turn structures. In this work we have investigated to what extent sequence context affects the severity with which inclusion of N6-methyladenine into different A:G base pairs of a standard k-turn affects RNA folding and L7Ae protein binding. We find that local sequence has a major influence, ranging from complete absence of folding and protein binding to a relatively mild effect. We have determined the crystal structure of one of these species both free and protein-bound, showing the environment of the methyl group and the way the modification is accommodated into the k-turn structure.
Original languageEnglish
Pages (from-to)1377-1385
Number of pages9
JournalRNA Biology
Volume16
Issue number10
Early online date24 Jun 2019
DOIs
Publication statusE-pub ahead of print - 24 Jun 2019

Fingerprint

Adenine
Protein Binding
Base Pairing
Methylation
RNA Folding
RNA
Carrier Proteins
Proteins

Keywords

  • RNA structure
  • RNA methylation
  • epigenetic modification
  • N6-methyladenine
  • kink-turn
  • X-ray crysallography

Cite this

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abstract = "N6-methyladenine is the most common covalent modification in cellular RNA species, with demonstrated functional consequences. At the molecular level this methylation could alter local RNA structure, and/or modulate the binding of specific proteins. We have previously shown that trans-Hoogsteen-sugar (sheared) A:G base pairs can be completely disrupted by methylation, and that this occurs in a sub-set of human box C/D k-turn structures. In this work we have investigated to what extent sequence context affects the severity with which inclusion of N6-methyladenine into different A:G base pairs of a standard k-turn affects RNA folding and L7Ae protein binding. We find that local sequence has a major influence, ranging from complete absence of folding and protein binding to a relatively mild effect. We have determined the crystal structure of one of these species both free and protein-bound, showing the environment of the methyl group and the way the modification is accommodated into the k-turn structure.",
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Effect of methylation of adenine N6 on kink turn structure depends on location. / Ashraf, Saira; Huang, Lin; Lilley, David (Lead / Corresponding author).

In: RNA Biology, Vol. 16, No. 10, 24.06.2019, p. 1377-1385.

Research output: Contribution to journalArticle

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T1 - Effect of methylation of adenine N6 on kink turn structure depends on location

AU - Ashraf, Saira

AU - Huang, Lin

AU - Lilley, David

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PY - 2019/6/24

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AB - N6-methyladenine is the most common covalent modification in cellular RNA species, with demonstrated functional consequences. At the molecular level this methylation could alter local RNA structure, and/or modulate the binding of specific proteins. We have previously shown that trans-Hoogsteen-sugar (sheared) A:G base pairs can be completely disrupted by methylation, and that this occurs in a sub-set of human box C/D k-turn structures. In this work we have investigated to what extent sequence context affects the severity with which inclusion of N6-methyladenine into different A:G base pairs of a standard k-turn affects RNA folding and L7Ae protein binding. We find that local sequence has a major influence, ranging from complete absence of folding and protein binding to a relatively mild effect. We have determined the crystal structure of one of these species both free and protein-bound, showing the environment of the methyl group and the way the modification is accommodated into the k-turn structure.

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