Understanding and Controlling RNA-protein Complexes Involved in Myotonic Dystrophy Type 1

Myotonic dystrophy is the most prevalent form of muscular dystrophy and its two forms (DM1 and DM2) affect approximately 1 in 8000 people. These diseases cannot be cured, and there are no treatment options that delay disease progression. Both diseases are caused by large expansions of repeated sequences of DNA, which is transcribed into long repeated sequences of RNA. These RNAs are toxic, as a number of cellular proteins associate with them and as a result, these proteins are not available to perform their normal functions. Chief among these proteins is muscleblind-like protein (MBNL).  In healthy cells, MBNL controls the correct expression of proteins that are important for a number of processes including relaxing muscles after contraction and insulin regulation. We have investigated the binding specificity, thermodynamics, and kinetics of the MBNL1 protein for toxic repeat RNA sequences and normal RNA target sites. We have also identified small molecules that will associate with the toxic repeat RNA and release MBNL.

Speaker: Anne Baranger, UC Berkeley