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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...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2010
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Materias: | |
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. |
format | Text |
id | pubmed-2965252 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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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