Structural insights into RNA recognition by the alternative-splicing regulator muscleblind-like MBNL1 Journal Article

   

Authors:	Teplova, M.; Patel, D. J.
Article Title:	Structural insights into RNA recognition by the alternative-splicing regulator muscleblind-like MBNL1
Abstract:	Muscleblind-like (MBNL) proteins, regulators of developmentally programmed alternative splicing, harbor tandem CCCH zinc-finger (ZnF) domains that target pre-mRNAs containing YGCU(U/G)Y sequence elements (where Y is a pyrimidine). In myotonic dystrophy, reduced levels of MBNL proteins lead to aberrant alternative splicing of a subset of pre-mRNAs. The crystal structure of MBNL1 ZnF3/4 bound to r(CGCUGU) establishes that both ZnF3 and ZnF4 target GC steps, with site-specific recognition mediated by a network of hydrogen bonds formed primarily with main chain groups of the protein. The relative alignment of ZnF3 and ZnF4 domains is dictated by the topology of the interdomain linker, with a resulting antiparallel orientation of bound GC elements, supportive of a chain-reversal loop trajectory for MBNL1-bound pre-mRNA targets. We anticipate that MBNL1-mediated targeting of looped RNA segments proximal to splice-site junctions could contribute to pre-mRNA alternative-splicing regulation. © 2008 Nature Publishing Group.
Keywords:	unclassified drug; nonhuman; protein domain; complex formation; protein binding; rna; rna-binding proteins; amino acid sequence; molecular sequence data; messenger rna; sequence alignment; molecular recognition; nucleotide sequence; recombinant protein; alternative rna splicing; crystal structure; hydrogen bond; models, molecular; crystallography, x-ray; protein structure, tertiary; protein deficiency; molecular interaction; gel mobility shift assay; protein structure, quaternary; zinc finger protein; complementary dna; rna precursors; stoichiometry; messenger rna precursor; protein rna binding; nitrogen nuclear magnetic resonance; myotonic dystrophy; mbnl1 protein; muscleblind like protein
Journal Title:	Nature Structural and Molecular Biology
Volume:	15
Issue:	12
ISSN:	1545-9993
Publisher:	Nature Publishing Group
Date Published:	2008-12-01
Start Page:	1343
End Page:	1351
Language:	English
DOI:	10.1038/nsmb.1519
PUBMED:	19043415
PROVIDER:	scopus
PMCID:	PMC4689322
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-57149097433&partnerID=40&md5=a94ceba5ef116f2686ac1bcaf5761178
Notes:	--- - "Cited By (since 1996): 22" - "Export Date: 17 November 2011" - "CODEN: NSMBC" - "Molecular Sequence Numbers: GENBANK: AAC01949, BAA24858, CAG31624, NP_510746;" - "Source: Scopus"

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