Identification of a Nuclear Exosome Decay Pathway for Processed Transcripts

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

Institut for Molekylærbiologi og Genetik - RNA-biologi og -innovation

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer 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.

Originalsprog	Engelsk
Tidsskrift	Molecular Cell
Vol/bind	64
Nummer	3
Sider (fra-til)	520-533
Antal sider	14
ISSN	1097-2765
DOI	https://doi.org/10.1016/j.molcel.2016.09.025
Status	Udgivet - 3 nov. 2016

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10.1016/j.molcel.2016.09.025

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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.",

keywords = "NEXT complex, PAXT connection, RNA exosome, nuclear RNA decay, poly(A) tail",

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

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doi = "10.1016/j.molcel.2016.09.025",

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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

AU - Pultz, Dennis

AU - Vitting-Seerup, Kristoffer

AU - Lykke-Andersen, Søren

AU - Andersen, Jens S

AU - Sandelin, Albin

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.

KW - NEXT complex

KW - PAXT connection

KW - RNA exosome

KW - nuclear RNA decay

KW - poly(A) tail

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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