RECOGNITION EVENTS IN RNA INTERFERENCE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Muscleblind-like (MBNL) proteins, regulators of developmentally programmed alternative splicing, harbor tandem CCCH Zn finger (ZnF) domains, that target pre-mRNAs containing YGCU(U/G)Y sequence elements. In myotonic dystrophy, reduced levels of MBNL proteins lead to aberrant alternative splicing of a subset of pre-mRNAs. To elucidate principles of the regulatory RNA elements recognition by MBNL we crystallized each MBNL1 tandem ZnF domain, ZnF1/2 and ZnF3/4, in the free form, and the structure of the second tandem ZnF3/4 bound to CGCUGU nucleotide.