title: The four Zn fingers of MBNL1 provide a flexible platform for recognition of its RNA binding elements.
abstract: BACKGROUND
  Muscleblind-like 1 (MBNL1) is an alternative splicing factor containing four CCCH Zinc fingers (ZnFs). The sequestration of MBNL1 by expanded CUG and CCUG repeats is a major component in causing myotonic dystrophy. In addition to binding the structured expanded CUG and CCUG repeats; previous results suggested that MBNL1 binds single-stranded RNAs containing GC dinucleotides.
  
  
  RESULTS
  We performed a systematic analysis of MBNL1 binding to single-stranded RNAs. These studies revealed that a single GC dinucleotide in poly-uridine is sufficient for MBNL1 binding and that a second GC dinucleotide confers higher affinity MBNL1 binding. However additional GC dinucleotides do not enhance RNA binding. We also showed that the RNA sequences adjacent to the GC dinucleotides play an important role in MBNL1 binding with the following preference: uridines >cytidines >adenosines >guanosines. For high affinity binding by MBNL1, the distance between the two GC dinucleotides can vary from 1 to 17 nucleotides.
  
  
  CONCLUSIONS
  These results suggest that MBNL1 is highly flexible and able to adopt different conformations to recognize RNAs with varying sequence configurations. Although MBNL1 contains four ZnFs, only two ZnF - GC dinucleotide interactions are necessary for high affinity binding.
authors.affiliation: Department of Chemistry, Reed College, Portland, OR 97202, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Cass
authors.forename: Rachel
authors.initials: R
authors.lastname: Hotchko
authors.forename: Paul
authors.initials: P
authors.lastname: Barber
authors.forename: Kimberly
authors.initials: K
authors.lastname: Jones
authors.forename: Devika P
authors.initials: DP
authors.lastname: Gates
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Berglund
mesh_terms: D001483:Base Sequence; D003597:Cytosine Nucleotides / Q000378:metabolism; D006150:Guanine Nucleotides / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D012313:RNA / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D003597:Cytosine Nucleotides; D006150:Guanine Nucleotides; C493663:MBNL1 protein, human; D016601:RNA-Binding Proteins; D012313:RNA