Structural basis for high-order complex of SARNP and DDX39B to facilitate mRNP assembly

Yihu Xie; Shengyan Gao; Ke Zhang; Prasanna Bhat; Bradley P. Clarke; Kimberly Batten; Menghan Mei; Matthew Gazzara; Jerry W. Shay; Kristen W. Lynch; Alexia E. Angelos; Pate S. Hill; Austin L. Ivey; Beatriz Fontoura; Yi Ren

doi:10.1016/j.celrep.2023.112988

Structural basis for high-order complex of SARNP and DDX39B to facilitate mRNP assembly

Yihu Xie, Shengyan Gao, Ke Zhang, Prasanna Bhat, Bradley P. Clarke, Kimberly Batten, Menghan Mei, Matthew Gazzara, Jerry W. Shay, Kristen W. Lynch, Alexia E. Angelos, Pate S. Hill, Austin L. Ivey, Beatriz Fontoura, Yi Ren

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

mRNA in eukaryotic cells is packaged into highly compacted ribonucleoprotein particles (mRNPs) in the nucleus and exported to the cytoplasm for translation. mRNP packaging and export require the evolutionarily conserved transcription-export (TREX) complex. TREX facilitates loading of various RNA-binding proteins on mRNA through the action of its DDX39B subunit. SARNP (Tho1 [transcriptional defect of Hpr1 by overexpression 1] in yeast) is shown to interact with DDX39B and affect mRNA export. The molecular mechanism of how SARNP recognizes DDX39B and functions in mRNP assembly is unclear. Here, we determine the crystal structure of a Tho1/DDX39B/RNA complex, revealing a multivalent interaction mediated by tandem DDX39B interacting motifs in SARNP/Tho1. The high-order complex of SARNP and DDX39B is evolutionarily conserved, and human SARNP can engage with five DDX39B molecules. RNA sequencing (RNA-seq) from SARNP knockdown cells shows the most affected RNAs in export are GC rich. Our work suggests the role of the high-order SARNP/DDX39B/RNA complex in mRNP assembly and export.

Original language	English (US)
Article number	112988
Journal	Cell Reports
Volume	42
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2023.112988
State	Published - Aug 29 2023

Keywords

CP: Molecular biology
DDX39B
DEAD-box ATPase
SARNP
Sub2
TREX complex
Tho1
UAP56
mRNA nuclear export
mRNP assembly

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2023.112988

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@article{4425eec1fd964dfcad6d4dfc3b1f1f1f,

title = "Structural basis for high-order complex of SARNP and DDX39B to facilitate mRNP assembly",

abstract = "mRNA in eukaryotic cells is packaged into highly compacted ribonucleoprotein particles (mRNPs) in the nucleus and exported to the cytoplasm for translation. mRNP packaging and export require the evolutionarily conserved transcription-export (TREX) complex. TREX facilitates loading of various RNA-binding proteins on mRNA through the action of its DDX39B subunit. SARNP (Tho1 [transcriptional defect of Hpr1 by overexpression 1] in yeast) is shown to interact with DDX39B and affect mRNA export. The molecular mechanism of how SARNP recognizes DDX39B and functions in mRNP assembly is unclear. Here, we determine the crystal structure of a Tho1/DDX39B/RNA complex, revealing a multivalent interaction mediated by tandem DDX39B interacting motifs in SARNP/Tho1. The high-order complex of SARNP and DDX39B is evolutionarily conserved, and human SARNP can engage with five DDX39B molecules. RNA sequencing (RNA-seq) from SARNP knockdown cells shows the most affected RNAs in export are GC rich. Our work suggests the role of the high-order SARNP/DDX39B/RNA complex in mRNP assembly and export.",

keywords = "CP: Molecular biology, DDX39B, DEAD-box ATPase, SARNP, Sub2, TREX complex, Tho1, UAP56, mRNA nuclear export, mRNP assembly",

author = "Yihu Xie and Shengyan Gao and Ke Zhang and Prasanna Bhat and Clarke, {Bradley P.} and Kimberly Batten and Menghan Mei and Matthew Gazzara and Shay, {Jerry W.} and Lynch, {Kristen W.} and Angelos, {Alexia E.} and Hill, {Pate S.} and Ivey, {Austin L.} and Beatriz Fontoura and Yi Ren",

note = "Funding Information: We thank the staff at the Life Sciences Collaborative Access Team beamline 21-ID-F and 21-ID-G at the Advanced Photon Source for help with X-ray data collection. This work was supported by NIH R35 GM133743 to Y.R., NIH R01 AI154635 to B.F., NIH R01 AI125524 to K.W.L. and B.F., and funds from Vanderbilt University School of Medicine to Y.R. . B.P.C. was supported by NIH / NCI training grant T32CA119925 . Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

month = aug,

day = "29",

doi = "10.1016/j.celrep.2023.112988",

language = "English (US)",

volume = "42",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "8",

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TY - JOUR

T1 - Structural basis for high-order complex of SARNP and DDX39B to facilitate mRNP assembly

AU - Xie, Yihu

AU - Gao, Shengyan

AU - Zhang, Ke

AU - Bhat, Prasanna

AU - Clarke, Bradley P.

AU - Batten, Kimberly

AU - Mei, Menghan

AU - Gazzara, Matthew

AU - Shay, Jerry W.

AU - Lynch, Kristen W.

AU - Angelos, Alexia E.

AU - Hill, Pate S.

AU - Ivey, Austin L.

AU - Fontoura, Beatriz

AU - Ren, Yi

N1 - Funding Information: We thank the staff at the Life Sciences Collaborative Access Team beamline 21-ID-F and 21-ID-G at the Advanced Photon Source for help with X-ray data collection. This work was supported by NIH R35 GM133743 to Y.R., NIH R01 AI154635 to B.F., NIH R01 AI125524 to K.W.L. and B.F., and funds from Vanderbilt University School of Medicine to Y.R. . B.P.C. was supported by NIH / NCI training grant T32CA119925 . Publisher Copyright: © 2023 The Author(s)

PY - 2023/8/29

Y1 - 2023/8/29

N2 - mRNA in eukaryotic cells is packaged into highly compacted ribonucleoprotein particles (mRNPs) in the nucleus and exported to the cytoplasm for translation. mRNP packaging and export require the evolutionarily conserved transcription-export (TREX) complex. TREX facilitates loading of various RNA-binding proteins on mRNA through the action of its DDX39B subunit. SARNP (Tho1 [transcriptional defect of Hpr1 by overexpression 1] in yeast) is shown to interact with DDX39B and affect mRNA export. The molecular mechanism of how SARNP recognizes DDX39B and functions in mRNP assembly is unclear. Here, we determine the crystal structure of a Tho1/DDX39B/RNA complex, revealing a multivalent interaction mediated by tandem DDX39B interacting motifs in SARNP/Tho1. The high-order complex of SARNP and DDX39B is evolutionarily conserved, and human SARNP can engage with five DDX39B molecules. RNA sequencing (RNA-seq) from SARNP knockdown cells shows the most affected RNAs in export are GC rich. Our work suggests the role of the high-order SARNP/DDX39B/RNA complex in mRNP assembly and export.

AB - mRNA in eukaryotic cells is packaged into highly compacted ribonucleoprotein particles (mRNPs) in the nucleus and exported to the cytoplasm for translation. mRNP packaging and export require the evolutionarily conserved transcription-export (TREX) complex. TREX facilitates loading of various RNA-binding proteins on mRNA through the action of its DDX39B subunit. SARNP (Tho1 [transcriptional defect of Hpr1 by overexpression 1] in yeast) is shown to interact with DDX39B and affect mRNA export. The molecular mechanism of how SARNP recognizes DDX39B and functions in mRNP assembly is unclear. Here, we determine the crystal structure of a Tho1/DDX39B/RNA complex, revealing a multivalent interaction mediated by tandem DDX39B interacting motifs in SARNP/Tho1. The high-order complex of SARNP and DDX39B is evolutionarily conserved, and human SARNP can engage with five DDX39B molecules. RNA sequencing (RNA-seq) from SARNP knockdown cells shows the most affected RNAs in export are GC rich. Our work suggests the role of the high-order SARNP/DDX39B/RNA complex in mRNP assembly and export.

KW - CP: Molecular biology

KW - DDX39B

KW - DEAD-box ATPase

KW - SARNP

KW - Sub2

KW - TREX complex

KW - Tho1

KW - UAP56

KW - mRNA nuclear export

KW - mRNP assembly

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U2 - 10.1016/j.celrep.2023.112988

DO - 10.1016/j.celrep.2023.112988

M3 - Article

C2 - 37578863

AN - SCOPUS:85167609191

SN - 2211-1247

VL - 42

JO - Cell Reports

JF - Cell Reports

IS - 8

M1 - 112988

ER -

Structural basis for high-order complex of SARNP and DDX39B to facilitate mRNP assembly

Abstract

Keywords

ASJC Scopus subject areas

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