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Identification of a nuclear exosome decay pathway for processed transcripts

ABSTRACT: The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its co-factor Mtr4p/hMTR4, which links to RNA-binding protein adaptors. One such activity is the human Nuclear EXosome Targeting (NEXT) complex, composed of hMTR4, the Zn-finger protein ZCCHC8 and the RNA-binding factor RBM7. NEXT primarily targets early and unprocessed transcripts, demanding a rationale for how the nuclear exosome recognizes processed RNAs. Here, we describe the PolyA tail eXosome Targeting (PAXT) connection, comprising the hitherto uncharacterized ZFC3H1 Zn-knuckle protein as a central link between hMTR4 and the nuclear polyA binding protein PABPN1. Individual depletion of ZFC3H1 and PABPN1 results in the accumulation of common transcripts, that are generally both longer and more 3’polyadenylated than NEXT substrates. Importantly, ZFC3H1/PABPN1 and ZCCHC8/RBM7 contact hMTR4 in a mutually exclusive manner, revealing that the exosome targets nuclear transcripts of different maturation status by substituting its hMTR4-associating adaptors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE84172 | GEO | 2016/11/03

SECONDARY ACCESSION(S): PRJNA328219

REPOSITORIES: GEO

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