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Nucleolin is important for Epstein-Barr virus nuclear antigen 1-mediated episome binding, maintenance, and transcription.
Proc Natl Acad Sci U S A. 2014 Jan 07; 111(1):243-8.PN

Abstract

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is essential for EBV episome maintenance, replication, and transcription. These effects are mediated by EBNA1 binding to cognate oriP DNA, which comprise 20 imperfect copies of a 30-bp dyad symmetry enhancer and an origin for DNA replication. To identify cell proteins essential for these EBNA1 functions, EBNA1 associated cell proteins were immune precipitated and analyzed by liquid chromatography-tandem mass spectrometry. Nucleolin (NCL) was identified to be EBNA1 associated. EBNA1's N-terminal 100 aa and NCL's RNA-binding domains were critical for EBNA1/NCL interaction. Lentivirus shRNA-mediated NCL depletion substantially reduced EBNA1 recruitment to oriP DNA, EBNA1-dependent transcription of an EBV oriP luciferase reporter, and EBV genome maintenance in lymphoblastoid cell lines. NCL RNA-binding domain K429 was critical for ATP and EBNA1 binding. NCL overexpression increased EBNA1 binding to oriP and transcription, whereas NCL K429A was deficient. Moreover, NCL silencing impaired lymphoblastoid cell line growth. These experiments reveal a surprisingly critical role for NCL K429 in EBNA1 episome maintenance and transcription, which may be a target for therapeutic intervention.

Authors+Show Affiliations

Department of Life Sciences, Tzu-Chi University, Hualien 97004, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24344309

Citation

Chen, Ya-Lin, et al. "Nucleolin Is Important for Epstein-Barr Virus Nuclear Antigen 1-mediated Episome Binding, Maintenance, and Transcription." Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 1, 2014, pp. 243-8.
Chen YL, Liu CD, Cheng CP, et al. Nucleolin is important for Epstein-Barr virus nuclear antigen 1-mediated episome binding, maintenance, and transcription. Proc Natl Acad Sci U S A. 2014;111(1):243-8.
Chen, Y. L., Liu, C. D., Cheng, C. P., Zhao, B., Hsu, H. J., Shen, C. L., Chiu, S. J., Kieff, E., & Peng, C. W. (2014). Nucleolin is important for Epstein-Barr virus nuclear antigen 1-mediated episome binding, maintenance, and transcription. Proceedings of the National Academy of Sciences of the United States of America, 111(1), 243-8. https://doi.org/10.1073/pnas.1321800111
Chen YL, et al. Nucleolin Is Important for Epstein-Barr Virus Nuclear Antigen 1-mediated Episome Binding, Maintenance, and Transcription. Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):243-8. PubMed PMID: 24344309.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nucleolin is important for Epstein-Barr virus nuclear antigen 1-mediated episome binding, maintenance, and transcription. AU - Chen,Ya-Lin, AU - Liu,Cheng-Der, AU - Cheng,Chi-Ping, AU - Zhao,Bo, AU - Hsu,Hao-Jen, AU - Shen,Chih-Long, AU - Chiu,Shu-Jun, AU - Kieff,Elliott, AU - Peng,Chih-wen, Y1 - 2013/12/16/ PY - 2013/12/18/entrez PY - 2013/12/18/pubmed PY - 2014/3/13/medline KW - chromatin KW - lymphoma KW - nasopharyngeal carcinoma KW - oncogenic herpesvirus SP - 243 EP - 8 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 111 IS - 1 N2 - Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is essential for EBV episome maintenance, replication, and transcription. These effects are mediated by EBNA1 binding to cognate oriP DNA, which comprise 20 imperfect copies of a 30-bp dyad symmetry enhancer and an origin for DNA replication. To identify cell proteins essential for these EBNA1 functions, EBNA1 associated cell proteins were immune precipitated and analyzed by liquid chromatography-tandem mass spectrometry. Nucleolin (NCL) was identified to be EBNA1 associated. EBNA1's N-terminal 100 aa and NCL's RNA-binding domains were critical for EBNA1/NCL interaction. Lentivirus shRNA-mediated NCL depletion substantially reduced EBNA1 recruitment to oriP DNA, EBNA1-dependent transcription of an EBV oriP luciferase reporter, and EBV genome maintenance in lymphoblastoid cell lines. NCL RNA-binding domain K429 was critical for ATP and EBNA1 binding. NCL overexpression increased EBNA1 binding to oriP and transcription, whereas NCL K429A was deficient. Moreover, NCL silencing impaired lymphoblastoid cell line growth. These experiments reveal a surprisingly critical role for NCL K429 in EBNA1 episome maintenance and transcription, which may be a target for therapeutic intervention. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/24344309/Nucleolin_is_important_for_Epstein_Barr_virus_nuclear_antigen_1_mediated_episome_binding_maintenance_and_transcription_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=24344309 DB - PRIME DP - Unbound Medicine ER -