Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy. Export

@article{citeulike:4211613, abstract = {Myotonic dystrophy (DM1) is an autosomal dominant neuromuscular disorder associated with a (CTG)(n) expansion in the 3'-untranslated region of the DM1 protein kinase (DMPK) gene. To explain disease pathogenesis, the RNA dominance model proposes that the DM1 mutation produces a gain-of-function at the RNA level in which CUG repeats form RNA hairpins that sequester nuclear factors required for proper muscle development and maintenance. Here, we identify the triplet repeat expansion (EXP) RNA-binding proteins as candidate sequestered factors. As predicted by the RNA dominance model, binding of the EXP proteins is specific for dsCUG RNAs and proportional to the size of the triplet repeat expansion. Remarkably, the EXP proteins are homologous to the Drosophila muscleblind proteins required for terminal differentiation of muscle and photoreceptor cells. EXP expression is also activated during mammalian myoblast differentiation, but the EXP proteins accumulate in nuclear foci in DM1 cells. We propose that DM1 disease is caused by aberrant recruitment of the EXP proteins to the DMPK transcript (CUG)(n) expansion.}, author = {Miller, J. W. and Urbinati, C. R. and Teng-Umnuay, P. and Stenberg, M. G. and Byrne, B. J. and Thornton, C. A. and Swanson, M. S.}, citeulike-article-id = {4211613}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/10970838}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=10970838}, day = {1}, issn = {0261-4189}, journal = {The EMBO journal}, keywords = {genetics\_paper, read, rna\_gain\_of\_function}, month = {September}, number = {17}, pages = {4439--4448}, posted-at = {2009-03-23 23:22:46}, priority = {0}, title = {Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/10970838}, volume = {19}, year = {2000} }

TY - JOUR ID - citeulike:4211613 L3 - citeulike-article-id:4211613 N2 - Myotonic dystrophy (DM1) is an autosomal dominant neuromuscular disorder associated with a (CTG)(n) expansion in the 3'-untranslated region of the DM1 protein kinase (DMPK) gene. To explain disease pathogenesis, the RNA dominance model proposes that the DM1 mutation produces a gain-of-function at the RNA level in which CUG repeats form RNA hairpins that sequester nuclear factors required for proper muscle development and maintenance. Here, we identify the triplet repeat expansion (EXP) RNA-binding proteins as candidate sequestered factors. As predicted by the RNA dominance model, binding of the EXP proteins is specific for dsCUG RNAs and proportional to the size of the triplet repeat expansion. Remarkably, the EXP proteins are homologous to the Drosophila muscleblind proteins required for terminal differentiation of muscle and photoreceptor cells. EXP expression is also activated during mammalian myoblast differentiation, but the EXP proteins accumulate in nuclear foci in DM1 cells. We propose that DM1 disease is caused by aberrant recruitment of the EXP proteins to the DMPK transcript (CUG)(n) expansion. IS - 17 JF - The EMBO journal SN - 0261-4189 EP - 4448 TI - Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy. VL - 19 SP - 4439 KW - genetics_paper KW - read KW - rna_gain_of_function AU - Miller, JW AU - Urbinati, CR AU - Teng-Umnuay, P AU - Stenberg, MG AU - Byrne, BJ AU - Thornton, CA AU - Swanson, MS PY - 2000/09/01/ UR - http://view.ncbi.nlm.nih.gov/pubmed/10970838 ER -