Work

Expansion of a CUG trinucleotide repeat in the 3′ untranslated region of myotonic dystrophy protein kinase transcripts results in nuclear retention of transcripts

Year: 1997

Type: article

Abstract: Expansion of a CTG trinucleotide repeat in the 3' untranslated region (UTR) of DMPK, the gene encoding myotonic dystrophy protein kinase, induces the dominantly inherited neuromuscular disorder myotonic dystrophy (DM). Transcripts containing the expanded trinucleotide are abundant in differentiated cultured myoblasts, and they are spliced and polyadenylylated normally. However, mutant transcripts never reach the cytoplasm in these nonmitotic cells; instead, they form stable clusters that are tightly linked to the nuclear matrix, which can prevent effective biochemical purification of these transcripts. In DM patients, reduced DMPK protein levels, consequent to nuclear retention of mutant transcripts, are probably a cause of disease development. Formation of nuclear foci is a novel mechanism for preventing transcript export and effecting a loss of gene function.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.94.14.7388

Authors: Brigid M. Davis, Mila E. McCurrach, Krishan L. Taneja, Robert H. Singer, David E. Housman

Institutions: Albert Einstein College of Medicine, University of Massachusetts Chan Medical School, Massachusetts Institute of Technology, Cold Spring Harbor Laboratory

Language: English

Topic: Genetic Neurodegenerative Diseases

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green