Identification of a nuclear exosome decay pathway for processed transcripts

TY - JOUR

T1 - Identification of a nuclear exosome decay pathway for processed transcripts

AU - Meola, Nicola

AU - Domanski, Michal

AU - Karadoulama, Evdoxia

AU - Chen, Yun

AU - Gentil, Coline Alice Jeanne

AU - Pultz, Dennis

AU - Vitting-Seerup, Kristoffer

AU - Lykke-Andersen, Søren

AU - Andersen, Jens S.

AU - Sandelin, Albin Gustav

AU - Jensen, Torben Heick

N1 - Copyright © 2016 Elsevier Inc. All rights reserved.

PY - 2016/11/3

Y1 - 2016/11/3

N2 - 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.

AB - 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.

U2 - 10.1016/j.molcel.2016.09.025

DO - 10.1016/j.molcel.2016.09.025

M3 - Journal article

C2 - 27871484

SN - 1097-2765

VL - 64

SP - 520

EP - 533

JO - Molecular Cell

JF - Molecular Cell

IS - 3

ER -