Structure of the RBM7-ZCCHC8 core of the NEXT complex reveals connections to splicing factors

Sebastian Falk; Ksenia Finogenova; Mireille Melko Sørensen; Christian Benda; Søren Lykke-Andersen; Torben Heick Jensen; Elena Conti

doi:10.1038/ncomms13573

Structure of the RBM7-ZCCHC8 core of the NEXT complex reveals connections to splicing factors

Sebastian Falk, Ksenia Finogenova, Mireille Melko Sørensen, Christian Benda, Søren Lykke-Andersen, Torben Heick Jensen, Elena Conti

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 eukaryotic RNA exosome participates extensively in RNA processing and degradation. In human cells, three accessory factors (RBM7, ZCCHC8 and hMTR4) interact to form the nuclear exosome targeting (NEXT) complex, which directs a subset of non-coding RNAs for exosomal degradation. Here we elucidate how RBM7 is incorporated in the NEXT complex. We identify a proline-rich segment of ZCCHC8 as the interaction site for the RNA-recognition motif (RRM) of RBM7 and present the crystal structure of the corresponding complex at 2.0 Å resolution. On the basis of the structure, we identify a proline-rich segment within the splicing factor SAP145 with strong similarity to ZCCHC8. We show that this segment of SAP145 not only binds the RRM region of another splicing factor SAP49 but also the RRM of RBM7. These dual interactions of RBM7 with the exosome and the spliceosome suggest a model whereby NEXT might recruit the exosome to degrade intronic RNAs.

Originalsprog	Engelsk
Artikelnummer	13573
Tidsskrift	Nature Communications
Vol/bind	7
Antal sider	10
ISSN	2041-1723
DOI	https://doi.org/10.1038/ncomms13573
Status	Udgivet - 1 dec. 2016

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10.1038/ncomms13573Licens: CC BY

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title = "Structure of the RBM7-ZCCHC8 core of the NEXT complex reveals connections to splicing factors",

abstract = "The eukaryotic RNA exosome participates extensively in RNA processing and degradation. In human cells, three accessory factors (RBM7, ZCCHC8 and hMTR4) interact to form the nuclear exosome targeting (NEXT) complex, which directs a subset of non-coding RNAs for exosomal degradation. Here we elucidate how RBM7 is incorporated in the NEXT complex. We identify a proline-rich segment of ZCCHC8 as the interaction site for the RNA-recognition motif (RRM) of RBM7 and present the crystal structure of the corresponding complex at 2.0 {\AA} resolution. On the basis of the structure, we identify a proline-rich segment within the splicing factor SAP145 with strong similarity to ZCCHC8. We show that this segment of SAP145 not only binds the RRM region of another splicing factor SAP49 but also the RRM of RBM7. These dual interactions of RBM7 with the exosome and the spliceosome suggest a model whereby NEXT might recruit the exosome to degrade intronic RNAs.",

author = "Sebastian Falk and Ksenia Finogenova and S{\o}rensen, {Mireille Melko} and Christian Benda and S{\o}ren Lykke-Andersen and Jensen, {Torben Heick} and Elena Conti",

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T1 - Structure of the RBM7-ZCCHC8 core of the NEXT complex reveals connections to splicing factors

AU - Falk, Sebastian

AU - Finogenova, Ksenia

AU - Sørensen, Mireille Melko

AU - Benda, Christian

AU - Lykke-Andersen, Søren

AU - Jensen, Torben Heick

AU - Conti, Elena

PY - 2016/12/1

Y1 - 2016/12/1

N2 - The eukaryotic RNA exosome participates extensively in RNA processing and degradation. In human cells, three accessory factors (RBM7, ZCCHC8 and hMTR4) interact to form the nuclear exosome targeting (NEXT) complex, which directs a subset of non-coding RNAs for exosomal degradation. Here we elucidate how RBM7 is incorporated in the NEXT complex. We identify a proline-rich segment of ZCCHC8 as the interaction site for the RNA-recognition motif (RRM) of RBM7 and present the crystal structure of the corresponding complex at 2.0 Å resolution. On the basis of the structure, we identify a proline-rich segment within the splicing factor SAP145 with strong similarity to ZCCHC8. We show that this segment of SAP145 not only binds the RRM region of another splicing factor SAP49 but also the RRM of RBM7. These dual interactions of RBM7 with the exosome and the spliceosome suggest a model whereby NEXT might recruit the exosome to degrade intronic RNAs.

AB - The eukaryotic RNA exosome participates extensively in RNA processing and degradation. In human cells, three accessory factors (RBM7, ZCCHC8 and hMTR4) interact to form the nuclear exosome targeting (NEXT) complex, which directs a subset of non-coding RNAs for exosomal degradation. Here we elucidate how RBM7 is incorporated in the NEXT complex. We identify a proline-rich segment of ZCCHC8 as the interaction site for the RNA-recognition motif (RRM) of RBM7 and present the crystal structure of the corresponding complex at 2.0 Å resolution. On the basis of the structure, we identify a proline-rich segment within the splicing factor SAP145 with strong similarity to ZCCHC8. We show that this segment of SAP145 not only binds the RRM region of another splicing factor SAP49 but also the RRM of RBM7. These dual interactions of RBM7 with the exosome and the spliceosome suggest a model whereby NEXT might recruit the exosome to degrade intronic RNAs.

U2 - 10.1038/ncomms13573

DO - 10.1038/ncomms13573

M3 - Journal article

C2 - 27905398

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 13573

ER -

Structure of the RBM7-ZCCHC8 core of the NEXT complex reveals connections to splicing factors

Abstract

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