Transcriptomics

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Alzheimer’s disease-associated U1 snRNP splicing dysfunction causes neuronal hyperexcitability and cognitive impairment [N40K neuron RNA-seq]


ABSTRACT: Recent proteome and transcriptome profiling of Alzheimer's disease (AD) brains reveals RNA splicing dysfunction and U1 small nuclear ribonucleoprotein (snRNP) pathology containing U1-70K and its N-terminal 40-KDa fragment (N40K). Here we present a causative role of U1 snRNP dysfunction to neurodegeneration in primary neurons and transgenic mice (N40K-Tg), in which N40K expression exerts a dominant-negative effect to downregulate full-length U1-70K. N40K-Tg recapitulates N40K insolubility, neuronal degeneration, cognitive impairment, and erroneous splicing events in synaptic pathways.

ORGANISM(S): Mus musculus

PROVIDER: GSE196872 | GEO | 2022/08/11

REPOSITORIES: GEO

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