Specific RNA interactions promote TDP-43 multivalent phase separation and maintain liquid properties

ABSTRACT: TDP-43 is an RNA binding protein that forms ribonucleoprotein condensates via liquid-liquid phase separation (LLPS) and regulates gene expression through specific RNA interactions. Loss of TDP-43 protein homeostasis and dysfunction are tied to neurodegenerative disorders, mainly amyotrophic lateral sclerosis and frontotemporal dementia. Alterations of TDP-43 LLPS properties may be linked to protein aggregation. However, the mechanisms regulating TDP-43 LLPS are ill-defined, particularly how TDP-43 association with specific RNA targets regulates TDP-43 condensation remains unclear. We show that RNA binding strongly promotes TDP-43 LLPS through sequence-specific interactions. RNA-driven condensation increases with the number of adjacent TDP-43 binding sites and is also mediated by multivalen

SUBMITTER: Mr. Zackary Grese 

PROVIDER: S-SCDT-EMBOR-2021-53632V1 | biostudies-other |

REPOSITORIES: biostudies-other