The genetic defect in DM1 is a mutated gene that is transcribed to mRNA with hundreds to thousands of CUG (cytosine-uridine-guanine) repeats, which form hairpin structures. CUG-repeat mRNA accumulates in nuclei, where it binds the protein muscleblind-1 (MBNL1). The interaction prevents MBNL1 from performing its normal function, RNA splicing. CUG-repeat mRNAs are a promising target for drug discovery because their repeat sequence is unique in the body. In July, neurologists Thurman M. Wheeler, Charles A. Thornton, and coworkers at the University of Rochester Medical Center reported having exploited this advantage by developing a short string of nucleotides that recognizes and binds CUG-repeat mRNA and consequently reduces DM1 symptoms in mice (C&EN, July 20, page 15; Science 2009, 325, 336).
by Stu Borman |
September 28, 2009