Identification of a nuclear exosome decay pathway for processed transcripts

Nicola Meola; Michal Domanski; Evdoxia Karadoulama; Yun Chen; Coline Alice Jeanne Gentil; Dennis Pultz; Kristoffer Vitting-Seerup; Søren Lykke-Andersen; Jens S. Andersen; Albin Gustav Sandelin; Torben Heick Jensen

doi:10.1016/j.molcel.2016.09.025

Identification of a nuclear exosome decay pathway for processed transcripts

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

Computational and RNA Biology

99 Citations (Scopus)

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.

Original language	English
Journal	Molecular Cell
Volume	64
Issue number	3
Pages (from-to)	520-533
Number of pages	14
ISSN	1097-2765
DOIs	https://doi.org/10.1016/j.molcel.2016.09.025
Publication status	Published - 3 Nov 2016

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title = "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 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.",

author = "Nicola Meola and Michal Domanski and Evdoxia Karadoulama and Yun Chen and Gentil, {Coline Alice Jeanne} and Dennis Pultz and Kristoffer Vitting-Seerup and S{\o}ren Lykke-Andersen and Andersen, {Jens S.} and Sandelin, {Albin Gustav} and Jensen, {Torben Heick}",

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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

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 -

Identification of a nuclear exosome decay pathway for processed transcripts

Abstract

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