Computational characterization of 3' splice variants in the GFAP isoform family.

Glial fibrillary acidic protein (GFAP) is an intermediate filament (IF) protein specific to central nervous system (CNS) astrocytes. It has been the subject of intense interest due to its association with neurodegenerative diseases, and because of growing evidence that IF proteins not only modulate...

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Autores principales:	Sarah E Boyd, Betina Nair, Sze Woei Ng, Jonathan M Keith, Jacqueline M Orian
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cfc5401563e948259b508298673091b6
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spelling	oai:doaj.org-article:cfc5401563e948259b508298673091b62021-11-18T07:23:42ZComputational characterization of 3' splice variants in the GFAP isoform family.1932-620310.1371/journal.pone.0033565https://doaj.org/article/cfc5401563e948259b508298673091b62012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22479412/?tool=EBIhttps://doaj.org/toc/1932-6203Glial fibrillary acidic protein (GFAP) is an intermediate filament (IF) protein specific to central nervous system (CNS) astrocytes. It has been the subject of intense interest due to its association with neurodegenerative diseases, and because of growing evidence that IF proteins not only modulate cellular structure, but also cellular function. Moreover, GFAP has a family of splicing isoforms apparently more complex than that of other CNS IF proteins, consistent with it possessing a range of functional and structural roles. The gene consists of 9 exons, and to date all isoforms associated with 3' end splicing have been identified from modifications within intron 7, resulting in the generation of exon 7a (GFAPδ/ε) and 7b (GFAPκ). To better understand the nature and functional significance of variation in this region, we used a Bayesian multiple change-point approach to identify conserved regions. This is the first successful application of this method to a single gene--it has previously only been used in whole-genome analyses. We identified several highly or moderately conserved regions throughout the intron 7/7a/7b regions, including untranslated regions and regulatory features, consistent with the biology of GFAP. Several putative unconfirmed features were also identified, including a possible new isoform. We then integrated multiple computational analyses on both the DNA and protein sequences from the mouse, rat and human, showing that the major isoform, GFAPα, has highly conserved structure and features across the three species, whereas the minor isoforms GFAPδ/ε and GFAPκ have low conservation of structure and features at the distal 3' end, both relative to each other and relative to GFAPα. The overall picture suggests distinct and tightly regulated functions for the 3' end isoforms, consistent with complex astrocyte biology. The results illustrate a computational approach for characterising splicing isoform families, using both DNA and protein sequences.Sarah E BoydBetina NairSze Woei NgJonathan M KeithJacqueline M OrianPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e33565 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sarah E Boyd Betina Nair Sze Woei Ng Jonathan M Keith Jacqueline M Orian Computational characterization of 3' splice variants in the GFAP isoform family.
description	Glial fibrillary acidic protein (GFAP) is an intermediate filament (IF) protein specific to central nervous system (CNS) astrocytes. It has been the subject of intense interest due to its association with neurodegenerative diseases, and because of growing evidence that IF proteins not only modulate cellular structure, but also cellular function. Moreover, GFAP has a family of splicing isoforms apparently more complex than that of other CNS IF proteins, consistent with it possessing a range of functional and structural roles. The gene consists of 9 exons, and to date all isoforms associated with 3' end splicing have been identified from modifications within intron 7, resulting in the generation of exon 7a (GFAPδ/ε) and 7b (GFAPκ). To better understand the nature and functional significance of variation in this region, we used a Bayesian multiple change-point approach to identify conserved regions. This is the first successful application of this method to a single gene--it has previously only been used in whole-genome analyses. We identified several highly or moderately conserved regions throughout the intron 7/7a/7b regions, including untranslated regions and regulatory features, consistent with the biology of GFAP. Several putative unconfirmed features were also identified, including a possible new isoform. We then integrated multiple computational analyses on both the DNA and protein sequences from the mouse, rat and human, showing that the major isoform, GFAPα, has highly conserved structure and features across the three species, whereas the minor isoforms GFAPδ/ε and GFAPκ have low conservation of structure and features at the distal 3' end, both relative to each other and relative to GFAPα. The overall picture suggests distinct and tightly regulated functions for the 3' end isoforms, consistent with complex astrocyte biology. The results illustrate a computational approach for characterising splicing isoform families, using both DNA and protein sequences.
format	article
author	Sarah E Boyd Betina Nair Sze Woei Ng Jonathan M Keith Jacqueline M Orian
author_facet	Sarah E Boyd Betina Nair Sze Woei Ng Jonathan M Keith Jacqueline M Orian
author_sort	Sarah E Boyd
title	Computational characterization of 3' splice variants in the GFAP isoform family.
title_short	Computational characterization of 3' splice variants in the GFAP isoform family.
title_full	Computational characterization of 3' splice variants in the GFAP isoform family.
title_fullStr	Computational characterization of 3' splice variants in the GFAP isoform family.
title_full_unstemmed	Computational characterization of 3' splice variants in the GFAP isoform family.
title_sort	computational characterization of 3' splice variants in the gfap isoform family.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/cfc5401563e948259b508298673091b6
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Computational characterization of 3' splice variants in the GFAP isoform family.

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