Ribosome Protein L4 is essential for Epstein-Barr Virus Nuclear Antigen 1 function

Chih Lung Shen; Cheng Der Liua; Ren In You; Yung Hao Ching; Jun Liang; Liangru Ke; Ya Lin Chen; Hong Chi Chen; Hao Jen Hsu; Je Wen Liou; Elliott Kieff; Chih Wen Peng

doi:10.1073/pnas.1525444113

Ribosome Protein L4 is essential for Epstein-Barr Virus Nuclear Antigen 1 function

Chih Lung Shen, Cheng Der Liua, Ren In You, Yung Hao Ching, Jun Liang, Liangru Ke, Ya Lin Chen, Hong Chi Chen, Hao Jen Hsu, Je Wen Liou, Elliott Kieff, Chih Wen Peng

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

24 Scopus citations

Abstract

Epstein-Barr Virus (EBV) Nuclear Antigen 1 (EBNA1)-mediated origin of plasmid replication (oriP) DNA episome maintenance is essential for EBV-mediated tumorigenesis. We have now found that EBNA1 binds to Ribosome Protein L4 (RPL4). RPL4 shRNA knockdown decreased EBNA1 activation of an oriP luciferase reporter, EBNA1 DNA binding in lymphoblastoid cell lines, and EBV genome number per lymphoblastoid cell line. EBV infection increased RPL4 expression and redistributed RPL4 to cell nuclei. RPL4 and Nucleolin (NCL) were a scaffold for an EBNA1-induced oriP complex. The RPL4 N terminus cooperated with NCL-K429 to support EBNA1 and oriPmediated episome binding and maintenance, whereas the NCL C-terminal K380 and K393 induced oriP DNA H3K4me2 modification and promoted EBNA1 activation of oriP-dependent transcription. These observations provide new insights into the mechanisms by which EBV uses NCL and RPL4 to establish persistent B-lymphoblastoid cell infection.

Original language	English
Pages (from-to)	2229-2234
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	113
Issue number	8
DOIs	https://doi.org/10.1073/pnas.1525444113
State	Published - 23 Feb 2016

Keywords

EBNA1
EBV
NCL
OriP
RPL4

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Shen, C. L., Liua, C. D., You, R. I., Ching, Y. H., Liang, J., Ke, L., Chen, Y. L., Chen, H. C., Hsu, H. J., Liou, J. W., Kieff, E., & Peng, C. W. (2016). Ribosome Protein L4 is essential for Epstein-Barr Virus Nuclear Antigen 1 function. Proceedings of the National Academy of Sciences of the United States of America, 113(8), 2229-2234. https://doi.org/10.1073/pnas.1525444113

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title = "Ribosome Protein L4 is essential for Epstein-Barr Virus Nuclear Antigen 1 function",

abstract = "Epstein-Barr Virus (EBV) Nuclear Antigen 1 (EBNA1)-mediated origin of plasmid replication (oriP) DNA episome maintenance is essential for EBV-mediated tumorigenesis. We have now found that EBNA1 binds to Ribosome Protein L4 (RPL4). RPL4 shRNA knockdown decreased EBNA1 activation of an oriP luciferase reporter, EBNA1 DNA binding in lymphoblastoid cell lines, and EBV genome number per lymphoblastoid cell line. EBV infection increased RPL4 expression and redistributed RPL4 to cell nuclei. RPL4 and Nucleolin (NCL) were a scaffold for an EBNA1-induced oriP complex. The RPL4 N terminus cooperated with NCL-K429 to support EBNA1 and oriPmediated episome binding and maintenance, whereas the NCL C-terminal K380 and K393 induced oriP DNA H3K4me2 modification and promoted EBNA1 activation of oriP-dependent transcription. These observations provide new insights into the mechanisms by which EBV uses NCL and RPL4 to establish persistent B-lymphoblastoid cell infection.",

keywords = "EBNA1, EBV, NCL, OriP, RPL4",

author = "Shen, {Chih Lung} and Liua, {Cheng Der} and You, {Ren In} and Ching, {Yung Hao} and Jun Liang and Liangru Ke and Chen, {Ya Lin} and Chen, {Hong Chi} and Hsu, {Hao Jen} and Liou, {Je Wen} and Elliott Kieff and Peng, {Chih Wen}",

note = "Funding Information: This work was supported by National Science Council Grant NSC 101-2320-B320-005-MY3, Ministry of Science and Technology Grant MOST 104-2320-B-320-013, and National Health Research Institutes Grants NHRI-EX-1025-9910BC and NHRI-EX103-10307BI (to C.-W.P.). E.K. was supported by National Institutes of Health Grants 5R01CA047006, 5R01CA085180, and 5R01CA170023.",

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doi = "10.1073/pnas.1525444113",

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T1 - Ribosome Protein L4 is essential for Epstein-Barr Virus Nuclear Antigen 1 function

AU - Shen, Chih Lung

AU - Liua, Cheng Der

AU - You, Ren In

AU - Ching, Yung Hao

AU - Liang, Jun

AU - Ke, Liangru

AU - Chen, Ya Lin

AU - Chen, Hong Chi

AU - Hsu, Hao Jen

AU - Liou, Je Wen

AU - Kieff, Elliott

AU - Peng, Chih Wen

N1 - Funding Information: This work was supported by National Science Council Grant NSC 101-2320-B320-005-MY3, Ministry of Science and Technology Grant MOST 104-2320-B-320-013, and National Health Research Institutes Grants NHRI-EX-1025-9910BC and NHRI-EX103-10307BI (to C.-W.P.). E.K. was supported by National Institutes of Health Grants 5R01CA047006, 5R01CA085180, and 5R01CA170023.

PY - 2016/2/23

Y1 - 2016/2/23

N2 - Epstein-Barr Virus (EBV) Nuclear Antigen 1 (EBNA1)-mediated origin of plasmid replication (oriP) DNA episome maintenance is essential for EBV-mediated tumorigenesis. We have now found that EBNA1 binds to Ribosome Protein L4 (RPL4). RPL4 shRNA knockdown decreased EBNA1 activation of an oriP luciferase reporter, EBNA1 DNA binding in lymphoblastoid cell lines, and EBV genome number per lymphoblastoid cell line. EBV infection increased RPL4 expression and redistributed RPL4 to cell nuclei. RPL4 and Nucleolin (NCL) were a scaffold for an EBNA1-induced oriP complex. The RPL4 N terminus cooperated with NCL-K429 to support EBNA1 and oriPmediated episome binding and maintenance, whereas the NCL C-terminal K380 and K393 induced oriP DNA H3K4me2 modification and promoted EBNA1 activation of oriP-dependent transcription. These observations provide new insights into the mechanisms by which EBV uses NCL and RPL4 to establish persistent B-lymphoblastoid cell infection.

AB - Epstein-Barr Virus (EBV) Nuclear Antigen 1 (EBNA1)-mediated origin of plasmid replication (oriP) DNA episome maintenance is essential for EBV-mediated tumorigenesis. We have now found that EBNA1 binds to Ribosome Protein L4 (RPL4). RPL4 shRNA knockdown decreased EBNA1 activation of an oriP luciferase reporter, EBNA1 DNA binding in lymphoblastoid cell lines, and EBV genome number per lymphoblastoid cell line. EBV infection increased RPL4 expression and redistributed RPL4 to cell nuclei. RPL4 and Nucleolin (NCL) were a scaffold for an EBNA1-induced oriP complex. The RPL4 N terminus cooperated with NCL-K429 to support EBNA1 and oriPmediated episome binding and maintenance, whereas the NCL C-terminal K380 and K393 induced oriP DNA H3K4me2 modification and promoted EBNA1 activation of oriP-dependent transcription. These observations provide new insights into the mechanisms by which EBV uses NCL and RPL4 to establish persistent B-lymphoblastoid cell infection.

KW - EBNA1

KW - EBV

KW - NCL

KW - OriP

KW - RPL4

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U2 - 10.1073/pnas.1525444113

DO - 10.1073/pnas.1525444113

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C2 - 26858444

AN - SCOPUS:84959253219

SN - 0027-8424

VL - 113

SP - 2229

EP - 2234

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 8

ER -

Ribosome Protein L4 is essential for Epstein-Barr Virus Nuclear Antigen 1 function

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