The RNA exosome complex degrades expanded hexanucleotide repeat RNA in C9orf72 FTLD/ALS

ABSTRACT: Nucleotide repeat expansions in the C9orf72 gene cause Frontotemporal Lobar Degeneration (FTLD) and Amyotrophic Lateral Sclerosis (ALS). Transcribed repeat RNA accumulates within RNA foci and is also translated into toxic dipeptide-repeat proteins (DPR). The mechanism of repeat RNA accumulation however remains unclear. The RNA exosome complex is a multimeric ribonuclease involved in degradation of defective RNA. Here we uncover the RNA exosome as a major degradation complex for pathogenic C9orf72-derived repeat RNA. Knockdown of EXOSC10, the catalytic subunit of the complex, enhanced repeat RNA and DPR protein expression levels. RNA degradation assays confirmed that EXOSC10 can degrade both sense and antisense repeats. Furthermore, EXOSC10 reduction increased RNA foci and repeat transcript

SUBMITTER: Dr. Yuya Kawabe 

PROVIDER: S-SCDT-EMBOJ-2019-102700 | biostudies-other |

REPOSITORIES: biostudies-other