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Heterogeneous Nuclear Ribonucleoprotein Particle A/B Proteins and the Control of Alternative Splicing of the Mammalian Heterogeneous Nuclear Ribonucleoprotein Particle A1 Pre-mRNA

  • Chapter
Regulation of Alternative Splicing

Part of the book series: Progress in Molecular and Subcellular Biology ((PMSB,volume 31))

Abstract

Mammalian pre-messenger RNAs (pre-mRNAs) interact with a distinct set of proteins to form heterogeneous nuclear ribonucleoprotein particles (hnRNPs). More than 25 different hnRNP proteins have been found associated with these complexes (Piñol-Roma et al. 1988; Dreyfuss et al. 1993). The core hnRNP proteins A1, A2, B1, B2, C1, and C2 are the most abundant species and are expressed in actively growing cells to levels that are comparable to core histones (Beyer et al. 1977; Kiledjian et al. 1994). Although several observations support the notion that core hnRNP proteins participate in pre-mRNA processing, the question of whether these proteins act in a sequence-independent or a sequence-specific manner is still a matter of debate (Abdul-Manan and Williams 1996; Abdul-Manan et al. 1996; McAfee et al. 1997). Early investigations have suggested that hnRNP proteins associate randomly with many different types of pre-mRNAs and ribopolymers to form particles sharing common structures and sedimentation properties (McKnight and Miller 1979; Lamb and Daneholt 1979; Pullman and Martin 1983; Thomas et al. 1983; Wilk et al. 1983). While the great abundance of core hnRNP proteins in the nucleus of growing cells (approximately 0.2 mM in a HeLa cell nucleus) can be taken as an argument in favor of generic RNA binding activity, it is unclear what fraction of this population of hnRNP proteins is free to interact with a nascent RNA sequence that exits the RNA polymerase II transcription complex. More recently, the use of antibodies recognizing individual hnRNP proteins has revealed that some hnRNP proteins can be deposited nonrandomly on nascent pre-mRNAs (Piñol-Roma et al. 1989; Matunis et al. 1993; Wurtz et al. 1996), suggesting that binding can be sequence-specific. Given the high abundance of hnRNP proteins and their ability to bind to many types of sequences with a range of affinities (Cobianchi et al. 1988; Conway et al. 1988; Piñol-Roma et al. 1988; LeStourgeon et al. 1990; Casas-Finet et al. 1993; Abdul-Manan and Williams 1996; Abdul-Manan et al. 1996), it has remained unclear to what extent the functions of core hnRNP proteins in nuclear RNA processing always depend on their ability to bind RNA in a sequence-specific manner.

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  1. M. J. Simard

    Present address: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, 01605, USA

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  1. Département de Microbiologie et d’Infectiologie, Faculté de Médecine, Université de Sherbrooke, Sherbrooke, Québec, Canada, J1H 5N4

    B. Chabot, C. LeBel, S. Hutchison, F. H. Nasim & M. J. Simard

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  2. C. LeBel
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  3. S. Hutchison
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  4. F. H. Nasim
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  1. Institute of Molecular Genetics of Montpellier, CNRS, 1919 Route de Mende, BP 5051, 34293, Montpellier Cedex 05, France

    Philippe Jeanteur

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Chabot, B., LeBel, C., Hutchison, S., Nasim, F.H., Simard, M.J. (2003). Heterogeneous Nuclear Ribonucleoprotein Particle A/B Proteins and the Control of Alternative Splicing of the Mammalian Heterogeneous Nuclear Ribonucleoprotein Particle A1 Pre-mRNA. In: Jeanteur, P. (eds) Regulation of Alternative Splicing. Progress in Molecular and Subcellular Biology, vol 31. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-09728-1_3

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