2. Academic Validation
  3. Identification of a Nuclear Exosome Decay Pathway for Processed Transcripts

Identification of a Nuclear Exosome Decay Pathway for Processed Transcripts

  • Mol Cell. 2016 Nov 3;64(3):520-533. doi: 10.1016/j.molcel.2016.09.025.
Nicola Meola 1,  Michal Domanski 1,  Evdoxia Karadoulama 2,  Yun Chen 3,  Coline Gentil 1,  Dennis Pultz 4,  Kristoffer Vitting-Seerup 3,  Søren Lykke-Andersen 1,  Jens S Andersen 4,  Albin Sandelin 3,  Torben Heick Jensen 5
Affiliations

Affiliations

  • 1 Department of Molecular Biology and Genetics, Aarhus University, C.F. Møllers Allé 3, Building 1130, DK-8000 Aarhus C, Denmark.
  • 2 Department of Molecular Biology and Genetics, Aarhus University, C.F. Møllers Allé 3, Building 1130, DK-8000 Aarhus C, Denmark; The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloesvej 5, DK-2200 Copenhagen, Denmark.
  • 3 The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloesvej 5, DK-2200 Copenhagen, Denmark.
  • 4 Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense, Denmark.
  • 5 Department of Molecular Biology and Genetics, Aarhus University, C.F. Møllers Allé 3, Building 1130, DK-8000 Aarhus C, Denmark. Electronic address: thj@mbg.au.dk.
PMID: 27871484 DOI: 10.1016/j.molcel.2016.09.025
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 example is the trimeric human nuclear exosome targeting (NEXT) complex, which is composed of hMTR4, the Zn-finger protein ZCCHC8, and the RNA-binding factor RBM7. NEXT primarily targets early and unprocessed transcripts, which demands a rationale for how the nuclear exosome recognizes processed RNAs. Here, we describe the poly(A) tail exosome targeting (PAXT) connection, which comprises the ZFC3H1 Zn-knuckle protein as a central link between hMTR4 and the nuclear poly(A)-binding protein PABPN1. Individual depletion of ZFC3H1 and PABPN1 results in the accumulation of common transcripts that are generally both longer and more extensively 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.

Keywords

NEXT complex; PAXT connection; RNA exosome; nuclear RNA decay; poly(A) tail.

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