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A novel RNA binding surface of the TAM domain of TIP5/BAZ2A mediates epigenetic regulation of rRNA genes.

Anosova I, Melnik S, Tripsianes K, Kateb F, Grummt I, Sattler M - Nucleic Acids Res. (2015)

Bottom Line: Here, we show that the NMR structure of the TAM domain of TIP5 resembles the fold of the MBD domain, found in methyl-CpG binding proteins.Mutation of critical amino acids within this surface abolishes RNA binding in vitro and in vivo.Our results explain the distinct binding specificities of TAM and MBD domains to RNA and methylated DNA, respectively, and reveal structural features for the interaction of NoRC with non-coding RNA.

View Article: PubMed Central - PubMed

Affiliation: Institute of Structural Biology, Helmholtz Zentrum München, Neuherberg D-85764, Germany Biomolecular NMR and Center for Integrated Protein Science Munich (CIPSM), Department Chemie, Technische Universität München, Garching D-85747, Germany.

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Comparison of TAM and MBD nucleic acid binding domains. (A) The pRNA binding surface of the TIP5/TAM domain. Side chains of residues important for RNA binding are shown on a cartoon representation of the TIP5/TAM domain structure. (B) Cartoon representation of the canonical MBD domain from MBD1 (light blue) in complex with methylated DNA shown as orange cartoon (PDB ID: 1IG4) (52).
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Figure 6: Comparison of TAM and MBD nucleic acid binding domains. (A) The pRNA binding surface of the TIP5/TAM domain. Side chains of residues important for RNA binding are shown on a cartoon representation of the TIP5/TAM domain structure. (B) Cartoon representation of the canonical MBD domain from MBD1 (light blue) in complex with methylated DNA shown as orange cartoon (PDB ID: 1IG4) (52).

Mentions: Canonical MBDs recognize methylated CpGs in DNA by hydrophobic residues located at the β-sheet surface, with additional DNA backbone contacts mediated by the extended loop L1 (52) (Figure 6). Although the fold of the TAM domain resembles the MBD domain, TAM does not exhibit binding preference for methylated DNA (Supplementary Figure S6). This may be explained by the fact that amino acids that mediate specific recognition of methylated CpG regions by the MBD domain are not conserved in the TAM domain (Figure 1b). Hence, the TIP5/TAM domain has evolved as a specific pRNA recognition domain that is required for NoRC recruitment to the rDNA promoter.


A novel RNA binding surface of the TAM domain of TIP5/BAZ2A mediates epigenetic regulation of rRNA genes.

Anosova I, Melnik S, Tripsianes K, Kateb F, Grummt I, Sattler M - Nucleic Acids Res. (2015)

Comparison of TAM and MBD nucleic acid binding domains. (A) The pRNA binding surface of the TIP5/TAM domain. Side chains of residues important for RNA binding are shown on a cartoon representation of the TIP5/TAM domain structure. (B) Cartoon representation of the canonical MBD domain from MBD1 (light blue) in complex with methylated DNA shown as orange cartoon (PDB ID: 1IG4) (52).
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Related In: Results  -  Collection

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Figure 6: Comparison of TAM and MBD nucleic acid binding domains. (A) The pRNA binding surface of the TIP5/TAM domain. Side chains of residues important for RNA binding are shown on a cartoon representation of the TIP5/TAM domain structure. (B) Cartoon representation of the canonical MBD domain from MBD1 (light blue) in complex with methylated DNA shown as orange cartoon (PDB ID: 1IG4) (52).
Mentions: Canonical MBDs recognize methylated CpGs in DNA by hydrophobic residues located at the β-sheet surface, with additional DNA backbone contacts mediated by the extended loop L1 (52) (Figure 6). Although the fold of the TAM domain resembles the MBD domain, TAM does not exhibit binding preference for methylated DNA (Supplementary Figure S6). This may be explained by the fact that amino acids that mediate specific recognition of methylated CpG regions by the MBD domain are not conserved in the TAM domain (Figure 1b). Hence, the TIP5/TAM domain has evolved as a specific pRNA recognition domain that is required for NoRC recruitment to the rDNA promoter.

Bottom Line: Here, we show that the NMR structure of the TAM domain of TIP5 resembles the fold of the MBD domain, found in methyl-CpG binding proteins.Mutation of critical amino acids within this surface abolishes RNA binding in vitro and in vivo.Our results explain the distinct binding specificities of TAM and MBD domains to RNA and methylated DNA, respectively, and reveal structural features for the interaction of NoRC with non-coding RNA.

View Article: PubMed Central - PubMed

Affiliation: Institute of Structural Biology, Helmholtz Zentrum München, Neuherberg D-85764, Germany Biomolecular NMR and Center for Integrated Protein Science Munich (CIPSM), Department Chemie, Technische Universität München, Garching D-85747, Germany.

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