Mutant huntingtin messenger RNA forms neuronal nuclear clusters in rodent and human brains.

ABSTRACT: Mutant messenger RNA (mRNA) and protein contribute to the clinical manifestation of many repeat-associated neurological disorders, with the presence of nuclear RNA clusters being a common pathological feature. Yet, investigations into Huntington's disease-caused by a CAG repeat expansion in exon 1 of the huntingtin (HTT) gene-have primarily focused on toxic protein gain-of-function as the primary disease-causing feature. To date, mutant HTT mRNA has not been identified as an in vivo hallmark of Huntington's disease. Here, we report that, in two Huntington's disease mouse models (YAC128 and BACHD-97Q-ΔN17), mutant HTT mRNA is retained in the nucleus. Widespread formation of large mRNA clusters (∼0.6-5 µm³) occurred in 50-75% of striatal and cort

SUBMITTER: Ly S 

PROVIDER: S-EPMC9707646 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature