Defining early steps in mRNA transport: Mutant mRNA in myotonic dystrophy type I is blocked at entry into SC-35 domains

  • Smith K
  • Byron M
  • Johnson C
 et al. 
  • 42


    Mendeley users who have this article in their library.
  • 38


    Citations of this article.


In myotonic dystrophy type 1 (DM1), triplet repeat expansion in the 3' untranslated region of dystrophia myotonica protein kinase (DMPK) causes the nuclear retention of mutant messenger RNA (mRNA). Although the DMPK gene locus positions precisely at the outer edge of a factor-rich SC-35 domain, the normal mRNA consistently accumulates within the domain, and this RNA is depleted upon transcriptional inhibition. In DM1, mutant transcripts detach from the gene but accumulate in granules that abut but do not enter SC-35 domains, suggesting that RNA entry into the domain is blocked. Despite their exclusion from these compartments, mutant transcripts are spliced. MBNL1 (muscleblind-like protein 1) is an alternative splicing factor that becomes highly concentrated with mutant RNA foci. Small interfering RNA-mediated knockdown of MBNL1 promotes the accumulation or entry of newly synthesized mutant transcripts in the SC-35 domain. Collectively, these data suggest that an initial step in the intranuclear path of some mRNAs is passage from the gene into an SC-35 domain and implicate these structures in postsplicing steps before export.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • Kelly P. Smith

  • Meg Byron

  • Carol Johnson

  • Yigong Xing

  • Jeanne B. Lawrence

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free