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Alternative splicing of CD200 is regulated by an exonic splicing enhancer and SF2/ASF

CD200, a type I membrane glycoprotein, plays an important role in prevention of inflammatory disorders, graft rejection, autoimmune diseases and spontaneous fetal loss. It also regulates tumor immunity. A truncated CD200 (CD200(tr)) resulting from alternative splicing has been identified and charact...

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Autores principales: Chen, Zhiqi, Ma, Xuezhong, Zhang, Jianhua, Hu, Jim, Gorczynski, Reginald M.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2010
Materias:
RNA
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2965252/
https://www.ncbi.nlm.nih.gov/pubmed/20558599
http://dx.doi.org/10.1093/nar/gkq554
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author Chen, Zhiqi
Ma, Xuezhong
Zhang, Jianhua
Hu, Jim
Gorczynski, Reginald M.
author_facet Chen, Zhiqi
Ma, Xuezhong
Zhang, Jianhua
Hu, Jim
Gorczynski, Reginald M.
author_sort Chen, Zhiqi
collection PubMed
description CD200, a type I membrane glycoprotein, plays an important role in prevention of inflammatory disorders, graft rejection, autoimmune diseases and spontaneous fetal loss. It also regulates tumor immunity. A truncated CD200 (CD200(tr)) resulting from alternative splicing has been identified and characterized as a functional antagonist to full-length CD200. Thus, it is important to explore the mechanism(s) controlling alternative splicing of CD200. In this study, we identified an exonic splicing enhancer (ESE) located in exon 2, which is a putative binding site for a splicing regulatory protein SF2/ASF. Deletion or mutation of the ESE site decreased expression of the full-length CD200. Direct binding of SF2/ASF to the ESE site was confirmed by RNA electrophoretic mobility shift assay (EMSA). Knockdown of expression of SF2/ASF resulted in the same splicing pattern as seen after deletion or mutation of the ESE, whereas overexpression of SF2/ASF increased expression of the full-length CD200. In vivo studies showed that viral infection reversed the alternative splicing pattern of CD200 with increased expression of SF2/ASF and the full-length CD200. Taken together, our data suggest for the first time that SF2/ASF regulates the function of CD200 by controlling CD200 alternative splicing, through direct binding to an ESE located in exon 2 of CD200.
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spelling pubmed-29652522010-10-28 Alternative splicing of CD200 is regulated by an exonic splicing enhancer and SF2/ASF Chen, Zhiqi Ma, Xuezhong Zhang, Jianhua Hu, Jim Gorczynski, Reginald M. Nucleic Acids Res RNA CD200, a type I membrane glycoprotein, plays an important role in prevention of inflammatory disorders, graft rejection, autoimmune diseases and spontaneous fetal loss. It also regulates tumor immunity. A truncated CD200 (CD200(tr)) resulting from alternative splicing has been identified and characterized as a functional antagonist to full-length CD200. Thus, it is important to explore the mechanism(s) controlling alternative splicing of CD200. In this study, we identified an exonic splicing enhancer (ESE) located in exon 2, which is a putative binding site for a splicing regulatory protein SF2/ASF. Deletion or mutation of the ESE site decreased expression of the full-length CD200. Direct binding of SF2/ASF to the ESE site was confirmed by RNA electrophoretic mobility shift assay (EMSA). Knockdown of expression of SF2/ASF resulted in the same splicing pattern as seen after deletion or mutation of the ESE, whereas overexpression of SF2/ASF increased expression of the full-length CD200. In vivo studies showed that viral infection reversed the alternative splicing pattern of CD200 with increased expression of SF2/ASF and the full-length CD200. Taken together, our data suggest for the first time that SF2/ASF regulates the function of CD200 by controlling CD200 alternative splicing, through direct binding to an ESE located in exon 2 of CD200. Oxford University Press 2010-10 2010-06-17 /pmc/articles/PMC2965252/ /pubmed/20558599 http://dx.doi.org/10.1093/nar/gkq554 Text en © The Author(s) 2010. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.5 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle RNA
Chen, Zhiqi
Ma, Xuezhong
Zhang, Jianhua
Hu, Jim
Gorczynski, Reginald M.
Alternative splicing of CD200 is regulated by an exonic splicing enhancer and SF2/ASF
title Alternative splicing of CD200 is regulated by an exonic splicing enhancer and SF2/ASF
title_full Alternative splicing of CD200 is regulated by an exonic splicing enhancer and SF2/ASF
title_fullStr Alternative splicing of CD200 is regulated by an exonic splicing enhancer and SF2/ASF
title_full_unstemmed Alternative splicing of CD200 is regulated by an exonic splicing enhancer and SF2/ASF
title_short Alternative splicing of CD200 is regulated by an exonic splicing enhancer and SF2/ASF
title_sort alternative splicing of cd200 is regulated by an exonic splicing enhancer and sf2/asf
topic RNA
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2965252/
https://www.ncbi.nlm.nih.gov/pubmed/20558599
http://dx.doi.org/10.1093/nar/gkq554
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