SRSF protein kinase 1 modulates RAN translation and suppresses CGG repeat toxicity

ABSTRACT: Transcribed CGG repeat expansions cause neurodegeneration in Fragile X-associated tremor/ataxia syndrome (FXTAS). CGG repeat RNAs sequester RNA-binding proteins (RBPs) into nuclear foci and undergo repeat-associated non-AUG (RAN) translation into toxic peptides. To identify proteins involved in these processes, we employed a CGG repeat RNA-tagging system to capture repeat associated RBPs by mass spectrometry in mammalian cells. We identified several SR (serine/arginine-rich) proteins that interact selectively with CGG repeats basally and under cellular stress. These proteins modify toxicity in a Drosophila model of FXTAS. Pharmacologic inhibition of serine/arginine protein kinases (SRPKs), which alter SRSF protein phosphorylation, localization and activity, directly inhibits RAN translatio

SUBMITTER: Dr. Indranil Malik 

PROVIDER: S-SCDT-EMM-2021-14163 | biostudies-other |

REPOSITORIES: biostudies-other