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Coupling Between Transcription and Alternative Splicing

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RNA and Cancer

Part of the book series: Cancer Treatment and Research ((CTAR,volume 158))

Abstract

The scenario of alternative splicing regulation is far more complex than the classical picture of a pre-mRNA being processed post-transcriptionally in more than one way. Introns are efficiently removed while transcripts are still being synthesized, supporting the idea of a co-transcriptional regulation of alternative splicing. Evidence of a functional coupling between splicing and transcription has recently emerged as it was observed that properties of one process may affect the outcome of the other. Co-transcriptionality is thought to improve splicing efficiency and kinetics by directing the nascent pre-mRNA into proper spliceosome assembly and favoring splicing factor recruitment. Two models have been proposed to explain the coupling of transcription and alternative splicing: in the recruitment model, promoters and pol II status affect the recruitment to the transcribing gene of splicing factors or bifunctional factors acting on both transcription and splicing; in the kinetic model, differences in the elongation rate of pol II would determine the timing in which splicing sites are presented, and thus the outcome of alternative splicing decisions. In the later model, chromatin structure has emerged as a key regulator. Although definitive evidence for transcriptionally coupled alternative splicing alterations in tumor development or cancer pathogenesis is still missing, many alternative splicing events altered in cancer might be subject to transcription-splicing coupling regulation.

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Acknowledgments

We thank the members of our lab and Anabella Srebrow for criticisms and helpful discussions. This work was supported by grants from the Fundación Antorchas, the Agencia Nacional de Promoción de Ciencia y Tecnología of Argentina, the European Union Network of Excellence on Alternative Splicing (EURASNET), and the University of Buenos Aires. I.E.S. and L.G.A. are recipients of fellowships from the Consejo Nacional de Investigaciones Científicas y Técnicas of Argentina (CONICET). A.R.K. is a Howard Hughes Medical Institute international research scholar and a career investigator of the CONICET.

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  1. Laboratorio de Fisiologia y Biologia Molecular, Departmento de Fisiologia, Biologia Molecular y Celular, IFIBYNE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, PAB. II, 20 Piso, Buenos Aires, 1428, Argentina

    Ignacio E. Schor, Luciana I. Gómez Acuña & Alberto R. Kornblihtt

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  1. Ignacio E. Schor
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  2. Luciana I. Gómez Acuña
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Correspondence to Alberto R. Kornblihtt .

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  1. Dept. of Neurology, Robert H. Lurie Cancer Center Center for Genetic Medicine, Chicago, Illinois, USA

    Jane Y. Wu

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Schor, I.E., Gómez Acuña, L.I., Kornblihtt, A.R. (2013). Coupling Between Transcription and Alternative Splicing. In: Wu, J. (eds) RNA and Cancer. Cancer Treatment and Research, vol 158. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-31659-3_1

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