Autoregulated splicing of muscleblind-like 1 (MBNL1) Pre-mRNA

J Biol Chem. 2011 Sep 30;286(39):34224-33. doi: 10.1074/jbc.M111.236547. Epub 2011 Aug 9.


Muscleblind-like 1 (MBNL1) is a splicing factor whose improper cellular localization is a central component of myotonic dystrophy. In myotonic dystrophy, the lack of properly localized MBNL1 leads to missplicing of many pre-mRNAs. One of these events is the aberrant inclusion of exon 5 within the MBNL1 pre-mRNA. The region of the MBNL1 gene that includes exon 5 and flanking intronic sequence is highly conserved in vertebrate genomes. The 3'-end of intron 4 is non-canonical in that it contains a predicted branch point that is 141 nucleotides from the 3'-splice site and an AAG 3'-splice site. Using a minigene that includes exon 4, intron 4, exon 5, intron 5, and exon 6 of MBNL1, we showed that MBNL1 regulates inclusion of exon 5. Mapping of the intron 4 branch point confirmed that branching occurs primarily at the predicted distant branch point. Structure probing and footprinting revealed that the highly conserved region between the branch point and 3'-splice site is primarily unstructured and that MBNL1 binds within this region of the pre-mRNA. Deletion of the MBNL1 response element eliminated MBNL1 splicing regulation and led to complete inclusion of exon 5, which is consistent with the suppressive effect of MBNL1 on splicing.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Exons / physiology*
  • HeLa Cells
  • Humans
  • Introns / physiology*
  • RNA Precursors / biosynthesis*
  • RNA Precursors / genetics
  • RNA Splice Sites / physiology*
  • RNA Splicing / physiology*
  • RNA-Binding Proteins / biosynthesis*
  • RNA-Binding Proteins / genetics
  • Response Elements / physiology


  • MBNL1 protein, human
  • RNA Precursors
  • RNA Splice Sites
  • RNA-Binding Proteins