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Int. J. Mol. Sci. 2015, 16(1), 1755-1771;

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

Institute of Genetics and Biophysics "Adriano Buzzati-Traverso", National Research Council, 80131 Naples, Italy
Department of Science and Technology, University of Naples "Parthenope", 80143 Naples, Italy
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Academic Editor: Akila Mayeda
Received: 3 November 2014 / Accepted: 26 December 2014 / Published: 13 January 2015
(This article belongs to the Special Issue Pre-mRNA Splicing)
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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. View Full-Text
Keywords: alternative splicing; RNA-sequencing; transcription factors; ZNF266; KRAB (Krüppel-associated box) domain alternative splicing; RNA-sequencing; transcription factors; ZNF266; KRAB (Krüppel-associated box) domain

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Scarpato, M.; Federico, A.; Ciccodicola, A.; Costa, V. Novel Transcription Factor Variants through RNA-Sequencing: The Importance of Being “Alternative”. Int. J. Mol. Sci. 2015, 16, 1755-1771.

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