MIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration.

ABSTRACT: The human genome expresses thousands of natural antisense transcripts (NAT) that can regulate epigenetic state, transcription, RNA stability or translation of their overlapping genes^1,2. Here we describe MAPT-AS1, a brain-enriched NAT that is conserved in primates and contains an embedded mammalian-wide interspersed repeat (MIR), which represses tau translation by competing for ribosomal RNA pairing with the MAPT mRNA internal ribosome entry site³. MAPT encodes tau, a neuronal intrinsically disordered protein (IDP) that stabilizes axonal microtubules. Hyperphosphorylated, aggregation-prone tau forms the hallmark inclusions of tauopathies⁴. Mutations in MAPT cause familial frontotemporal dementia, and common variations forming the MAPT H1 haplotype are a sig

SUBMITTER: Simone R 

PROVIDER: S-EPMC7610982 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature