Interaction profiling identifies the human nuclear exosome targeting complex

Michal Szymon Lubas, Marianne Spangsberg Christensen, Maiken Søndergaard Kristiansen, Michal Domanski, Lasse G Falkenby, Søren Lykke-Andersen, Jens S. Andersen, Andrzej Dziembowski, Torben Heick Jensen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

The RNA exosome is a conserved degradation machinery, which obtains full activity only when associated with cofactors. The most prominent activator of the yeast nuclear exosome is the RNA helicase Mtr4p, acting in the context of the Trf4p/Air2p/Mtr4p polyadenylation (TRAMP) complex. The existence of a similar activator(s) in humans remains elusive. By establishing an interaction network of the human nuclear exosome, we identify the trimeric Nuclear Exosome Targeting (NEXT) complex, containing hMTR4, the Zn-knuckle protein ZCCHC8, and the putative RNA binding protein RBM7. ZCCHC8 and RBM7 are excluded from nucleoli, and consistently NEXT is specifically required for the exosomal degradation of promoter upstream transcripts (PROMPTs). We also detect putative homolog TRAMP subunits hTRF4-2 (Trf4p) and ZCCHC7 (Air2p) in hRRP6 and hMTR4 precipitates. However, at least ZCCHC7 function is restricted to nucleoli. Our results suggest that human nuclear exosome degradation pathways comprise modules of spatially organized cofactors that diverge from the yeast model.
OriginalsprogEngelsk
TidsskriftMolecular Cell
Vol/bind43
Udgave nummer4
Sider (fra-til)624-37
Antal sider14
ISSN1097-2765
DOI
StatusUdgivet - 19. aug. 2011

Fingeraftryk

Exosomes
Polyadenylation
Proteins

Citer dette

Lubas, M. S., Christensen, M. S., Kristiansen, M. S., Domanski, M., Falkenby, L. G., Lykke-Andersen, S., ... Jensen, T. H. (2011). Interaction profiling identifies the human nuclear exosome targeting complex. Molecular Cell, 43(4), 624-37. https://doi.org/10.1016/j.molcel.2011.06.028
Lubas, Michal Szymon ; Christensen, Marianne Spangsberg ; Kristiansen, Maiken Søndergaard ; Domanski, Michal ; Falkenby, Lasse G ; Lykke-Andersen, Søren ; Andersen, Jens S. ; Dziembowski, Andrzej ; Jensen, Torben Heick. / Interaction profiling identifies the human nuclear exosome targeting complex. I: Molecular Cell. 2011 ; Bind 43, Nr. 4. s. 624-37.
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abstract = "The RNA exosome is a conserved degradation machinery, which obtains full activity only when associated with cofactors. The most prominent activator of the yeast nuclear exosome is the RNA helicase Mtr4p, acting in the context of the Trf4p/Air2p/Mtr4p polyadenylation (TRAMP) complex. The existence of a similar activator(s) in humans remains elusive. By establishing an interaction network of the human nuclear exosome, we identify the trimeric Nuclear Exosome Targeting (NEXT) complex, containing hMTR4, the Zn-knuckle protein ZCCHC8, and the putative RNA binding protein RBM7. ZCCHC8 and RBM7 are excluded from nucleoli, and consistently NEXT is specifically required for the exosomal degradation of promoter upstream transcripts (PROMPTs). We also detect putative homolog TRAMP subunits hTRF4-2 (Trf4p) and ZCCHC7 (Air2p) in hRRP6 and hMTR4 precipitates. However, at least ZCCHC7 function is restricted to nucleoli. Our results suggest that human nuclear exosome degradation pathways comprise modules of spatially organized cofactors that diverge from the yeast model.",
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Lubas, MS, Christensen, MS, Kristiansen, MS, Domanski, M, Falkenby, LG, Lykke-Andersen, S, Andersen, JS, Dziembowski, A & Jensen, TH 2011, 'Interaction profiling identifies the human nuclear exosome targeting complex', Molecular Cell, bind 43, nr. 4, s. 624-37. https://doi.org/10.1016/j.molcel.2011.06.028

Interaction profiling identifies the human nuclear exosome targeting complex. / Lubas, Michal Szymon; Christensen, Marianne Spangsberg; Kristiansen, Maiken Søndergaard; Domanski, Michal; Falkenby, Lasse G; Lykke-Andersen, Søren; Andersen, Jens S.; Dziembowski, Andrzej; Jensen, Torben Heick.

I: Molecular Cell, Bind 43, Nr. 4, 19.08.2011, s. 624-37.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Interaction profiling identifies the human nuclear exosome targeting complex

AU - Lubas, Michal Szymon

AU - Christensen, Marianne Spangsberg

AU - Kristiansen, Maiken Søndergaard

AU - Domanski, Michal

AU - Falkenby, Lasse G

AU - Lykke-Andersen, Søren

AU - Andersen, Jens S.

AU - Dziembowski, Andrzej

AU - Jensen, Torben Heick

N1 - Copyright © 2011 Elsevier Inc. All rights reserved.

PY - 2011/8/19

Y1 - 2011/8/19

N2 - The RNA exosome is a conserved degradation machinery, which obtains full activity only when associated with cofactors. The most prominent activator of the yeast nuclear exosome is the RNA helicase Mtr4p, acting in the context of the Trf4p/Air2p/Mtr4p polyadenylation (TRAMP) complex. The existence of a similar activator(s) in humans remains elusive. By establishing an interaction network of the human nuclear exosome, we identify the trimeric Nuclear Exosome Targeting (NEXT) complex, containing hMTR4, the Zn-knuckle protein ZCCHC8, and the putative RNA binding protein RBM7. ZCCHC8 and RBM7 are excluded from nucleoli, and consistently NEXT is specifically required for the exosomal degradation of promoter upstream transcripts (PROMPTs). We also detect putative homolog TRAMP subunits hTRF4-2 (Trf4p) and ZCCHC7 (Air2p) in hRRP6 and hMTR4 precipitates. However, at least ZCCHC7 function is restricted to nucleoli. Our results suggest that human nuclear exosome degradation pathways comprise modules of spatially organized cofactors that diverge from the yeast model.

AB - The RNA exosome is a conserved degradation machinery, which obtains full activity only when associated with cofactors. The most prominent activator of the yeast nuclear exosome is the RNA helicase Mtr4p, acting in the context of the Trf4p/Air2p/Mtr4p polyadenylation (TRAMP) complex. The existence of a similar activator(s) in humans remains elusive. By establishing an interaction network of the human nuclear exosome, we identify the trimeric Nuclear Exosome Targeting (NEXT) complex, containing hMTR4, the Zn-knuckle protein ZCCHC8, and the putative RNA binding protein RBM7. ZCCHC8 and RBM7 are excluded from nucleoli, and consistently NEXT is specifically required for the exosomal degradation of promoter upstream transcripts (PROMPTs). We also detect putative homolog TRAMP subunits hTRF4-2 (Trf4p) and ZCCHC7 (Air2p) in hRRP6 and hMTR4 precipitates. However, at least ZCCHC7 function is restricted to nucleoli. Our results suggest that human nuclear exosome degradation pathways comprise modules of spatially organized cofactors that diverge from the yeast model.

U2 - 10.1016/j.molcel.2011.06.028

DO - 10.1016/j.molcel.2011.06.028

M3 - Journal article

C2 - 21855801

VL - 43

SP - 624

EP - 637

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 4

ER -

Lubas MS, Christensen MS, Kristiansen MS, Domanski M, Falkenby LG, Lykke-Andersen S et al. Interaction profiling identifies the human nuclear exosome targeting complex. Molecular Cell. 2011 aug 19;43(4):624-37. https://doi.org/10.1016/j.molcel.2011.06.028