Identification of a Nuclear Exosome Decay Pathway for Processed Transcripts

Nicola Meola, Michal Domanski, Evdoxia Karadoulama, Yun Chen, Coline Gentil, D. Pultz, Kristoffer Vitting-Seerup, Søren Lykke-Andersen, J. S. Andersen, Albin Gustav Sandelin, Torben Heick Jensen

Research output: Contribution to journalJournal articleResearchpeer-review

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. © 2016 Elsevier Inc.
Original languageEnglish
JournalMolecular Cell
Volume64
Issue number3
Pages (from-to)520-533
ISSN1097-2765
DOIs
Publication statusPublished - 2016

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