UMMS Affiliation

Department of Cell Biology

Date

9-12-2007

Document Type

Article

Subjects

Cells, Cultured; Child; Humans; Male; Models, Molecular; Mutation; Myoblasts, Skeletal; Myotonic Dystrophy; Protein Structure, Tertiary; Protein-Serine-Threonine Kinases; *RNA Splicing; RNA Transport; RNA, Messenger; RNA-Binding Proteins; Trinucleotide Repeat Expansion

Disciplines

Cell Biology | Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: J Cell Biol. 2007 Sep 10;178(6):951-64. Link to article on publisher's site

DOI of Published Version

10.1083/jcb.200706048

Related Resources

Link to Article in PubMed

Journal Title

The Journal of cell biology

PubMed ID

17846170

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