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Novel Transcription Factor Variants through RNA-Sequencing: The Importance of Being “Alternative”

Alternative splicing is a pervasive mechanism of RNA maturation in higher eukaryotes, which increases proteomic diversity and biological complexity. It has a key regulatory role in several physiological and pathological states. The diffusion of Next Generation Sequencing, particularly of RNA-Sequenc...

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Detalles Bibliográficos
Autores principales: Scarpato, Margherita, Federico, Antonio, Ciccodicola, Alfredo, Costa, Valerio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307332/
https://www.ncbi.nlm.nih.gov/pubmed/25590302
http://dx.doi.org/10.3390/ijms16011755
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author Scarpato, Margherita
Federico, Antonio
Ciccodicola, Alfredo
Costa, Valerio
author_facet Scarpato, Margherita
Federico, Antonio
Ciccodicola, Alfredo
Costa, Valerio
author_sort Scarpato, Margherita
collection PubMed
description Alternative splicing is a pervasive mechanism of RNA maturation in higher eukaryotes, which increases proteomic diversity and biological complexity. It has a key regulatory role in several physiological and pathological states. The diffusion of Next Generation Sequencing, particularly of RNA-Sequencing, has exponentially empowered the identification of novel transcripts revealing that more than 95% of human genes undergo alternative splicing. The highest rate of alternative splicing occurs in transcription factors encoding genes, mostly in Krüppel-associated box domains of zinc finger proteins. Since these molecules are responsible for gene expression, alternative splicing is a crucial mechanism to “regulate the regulators”. Indeed, different transcription factors isoforms may have different or even opposite functions. In this work, through a targeted re-analysis of our previously published RNA-Sequencing datasets, we identified nine novel transcripts in seven transcription factors genes. In silico analysis, combined with RT-PCR, cloning and Sanger sequencing, allowed us to experimentally validate these new variants. Through computational approaches we also predicted their novel structural and functional properties. Our findings indicate that alternative splicing is a major determinant of transcription factor diversity, confirming that accurate analysis of RNA-Sequencing data can reliably lead to the identification of novel transcripts, with potentially new functions.
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spelling pubmed-43073322015-02-02 Novel Transcription Factor Variants through RNA-Sequencing: The Importance of Being “Alternative” Scarpato, Margherita Federico, Antonio Ciccodicola, Alfredo Costa, Valerio Int J Mol Sci Article Alternative splicing is a pervasive mechanism of RNA maturation in higher eukaryotes, which increases proteomic diversity and biological complexity. It has a key regulatory role in several physiological and pathological states. The diffusion of Next Generation Sequencing, particularly of RNA-Sequencing, has exponentially empowered the identification of novel transcripts revealing that more than 95% of human genes undergo alternative splicing. The highest rate of alternative splicing occurs in transcription factors encoding genes, mostly in Krüppel-associated box domains of zinc finger proteins. Since these molecules are responsible for gene expression, alternative splicing is a crucial mechanism to “regulate the regulators”. Indeed, different transcription factors isoforms may have different or even opposite functions. In this work, through a targeted re-analysis of our previously published RNA-Sequencing datasets, we identified nine novel transcripts in seven transcription factors genes. In silico analysis, combined with RT-PCR, cloning and Sanger sequencing, allowed us to experimentally validate these new variants. Through computational approaches we also predicted their novel structural and functional properties. Our findings indicate that alternative splicing is a major determinant of transcription factor diversity, confirming that accurate analysis of RNA-Sequencing data can reliably lead to the identification of novel transcripts, with potentially new functions. MDPI 2015-01-13 /pmc/articles/PMC4307332/ /pubmed/25590302 http://dx.doi.org/10.3390/ijms16011755 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Scarpato, Margherita
Federico, Antonio
Ciccodicola, Alfredo
Costa, Valerio
Novel Transcription Factor Variants through RNA-Sequencing: The Importance of Being “Alternative”
title Novel Transcription Factor Variants through RNA-Sequencing: The Importance of Being “Alternative”
title_full Novel Transcription Factor Variants through RNA-Sequencing: The Importance of Being “Alternative”
title_fullStr Novel Transcription Factor Variants through RNA-Sequencing: The Importance of Being “Alternative”
title_full_unstemmed Novel Transcription Factor Variants through RNA-Sequencing: The Importance of Being “Alternative”
title_short Novel Transcription Factor Variants through RNA-Sequencing: The Importance of Being “Alternative”
title_sort novel transcription factor variants through rna-sequencing: the importance of being “alternative”
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307332/
https://www.ncbi.nlm.nih.gov/pubmed/25590302
http://dx.doi.org/10.3390/ijms16011755
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