Progress Update: Consequence of human satellite II repeat expression in FSHD

Posted by Friends of FSH Research on Jan 30, 2024

Report by Tessa Arends
See grant Consequence of human satellite II repeat expression in FSHD

My research addresses a major mechanism driving DUX4-induced cellular toxicity in skeletal muscle, the formation and aggregation of RNA-protein complexes. Prior studies have shown that DUX4-expressing muscle cells form nuclear protein aggregates. Our lab has shown that DUX4 induces the accumulation of HSATII RNA which sequesters nuclear proteins and contributes to DUX4-mediated cellular toxicity in muscle cells. However, whether HSATII RNA is responsible for all protein aggregation or just sequesters a subset of proteins in DUX4-expressing muscle cells remains unclear. My work has uncovered that DUX4 induces the accumulation of other stable nuclear RNAs, which includes HSATII, that sequester distinct RNA binding proteins. This suggests that HSATII-derived ribonucleoprotein (RNP) complexes and non-HSATII RNA-derived RNP complexes may have non-overlapping functions and consequences on the cell.