RNA-Sequencing data supports the existence of novel VEGFA splicing events but not of VEGFAxxxb isoforms

Abstract Vascular endothelial growth factor (VEGFA), a pivotal regulator of angiogenesis and valuable therapeutic target, is characterised by alternative splicing which generates three principal isoforms, VEGFA121, VEGFA165 and VEGFA189. A second set of anti-angiogenic isoforms termed VEGFAxxxb that...

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Autores principales:	Stephen Bridgett, Margaret Dellett, David A. Simpson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a903cee8d8004fe48b45ecb0d3a60fde
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spelling	oai:doaj.org-article:a903cee8d8004fe48b45ecb0d3a60fde2021-12-02T15:06:07ZRNA-Sequencing data supports the existence of novel VEGFA splicing events but not of VEGFAxxxb isoforms10.1038/s41598-017-00100-32045-2322https://doaj.org/article/a903cee8d8004fe48b45ecb0d3a60fde2017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00100-3https://doaj.org/toc/2045-2322Abstract Vascular endothelial growth factor (VEGFA), a pivotal regulator of angiogenesis and valuable therapeutic target, is characterised by alternative splicing which generates three principal isoforms, VEGFA121, VEGFA165 and VEGFA189. A second set of anti-angiogenic isoforms termed VEGFAxxxb that utilise an alternative splice site in the final exon have been widely reported, with mRNA detection based principally upon RT-PCR assays. We sought confirmation of the existence of the VEGFAxxxb isoforms within the abundant RNA sequencing data available publicly. Whilst sequences derived specifically from each of the canonical VEGFA isoforms were present in many tissues, there were no sequences derived from VEGFAxxxb isoforms. Sequencing of approximately 50,000 RT-PCR products spanning the exon 7–8 junction in 10 tissues did not identify any VEGFAxxxb transcripts. The absence or extremely low expression of these transcripts in vivo indicates that VEGFAxxxb isoforms are unlikely to play a role in normal physiology. Our analyses also revealed multiple novel splicing events supported by more reads than previously reported for VEGFA145 and VEGFA148 isoforms, including three from novel first exons consistent with existing transcription start site data. These novel VEGFA isoforms may play significant roles in specific cell types.Stephen BridgettMargaret DellettDavid A. SimpsonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stephen Bridgett Margaret Dellett David A. Simpson RNA-Sequencing data supports the existence of novel VEGFA splicing events but not of VEGFAxxxb isoforms
description	Abstract Vascular endothelial growth factor (VEGFA), a pivotal regulator of angiogenesis and valuable therapeutic target, is characterised by alternative splicing which generates three principal isoforms, VEGFA121, VEGFA165 and VEGFA189. A second set of anti-angiogenic isoforms termed VEGFAxxxb that utilise an alternative splice site in the final exon have been widely reported, with mRNA detection based principally upon RT-PCR assays. We sought confirmation of the existence of the VEGFAxxxb isoforms within the abundant RNA sequencing data available publicly. Whilst sequences derived specifically from each of the canonical VEGFA isoforms were present in many tissues, there were no sequences derived from VEGFAxxxb isoforms. Sequencing of approximately 50,000 RT-PCR products spanning the exon 7–8 junction in 10 tissues did not identify any VEGFAxxxb transcripts. The absence or extremely low expression of these transcripts in vivo indicates that VEGFAxxxb isoforms are unlikely to play a role in normal physiology. Our analyses also revealed multiple novel splicing events supported by more reads than previously reported for VEGFA145 and VEGFA148 isoforms, including three from novel first exons consistent with existing transcription start site data. These novel VEGFA isoforms may play significant roles in specific cell types.
format	article
author	Stephen Bridgett Margaret Dellett David A. Simpson
author_facet	Stephen Bridgett Margaret Dellett David A. Simpson
author_sort	Stephen Bridgett
title	RNA-Sequencing data supports the existence of novel VEGFA splicing events but not of VEGFAxxxb isoforms
title_short	RNA-Sequencing data supports the existence of novel VEGFA splicing events but not of VEGFAxxxb isoforms
title_full	RNA-Sequencing data supports the existence of novel VEGFA splicing events but not of VEGFAxxxb isoforms
title_fullStr	RNA-Sequencing data supports the existence of novel VEGFA splicing events but not of VEGFAxxxb isoforms
title_full_unstemmed	RNA-Sequencing data supports the existence of novel VEGFA splicing events but not of VEGFAxxxb isoforms
title_sort	rna-sequencing data supports the existence of novel vegfa splicing events but not of vegfaxxxb isoforms
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a903cee8d8004fe48b45ecb0d3a60fde
work_keys_str_mv	AT stephenbridgett rnasequencingdatasupportstheexistenceofnovelvegfasplicingeventsbutnotofvegfaxxxbisoforms AT margaretdellett rnasequencingdatasupportstheexistenceofnovelvegfasplicingeventsbutnotofvegfaxxxbisoforms AT davidasimpson rnasequencingdatasupportstheexistenceofnovelvegfasplicingeventsbutnotofvegfaxxxbisoforms
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RNA-Sequencing data supports the existence of novel VEGFA splicing events but not of VEGFAxxxb isoforms

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