Encyclopedia of Biophysics

Living Edition
| Editors: Gordon Roberts, Anthony Watts, European Biophysical Societies

Alternative Splicing Regulation: Structural and Biophysical Studies

  • André Mourão
  • Michael SattlerEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-3-642-35943-9_446-1

Definition

Alternative splicing (AS) is the process, by which multiple messenger RNAs are synthesized from a single gene and thereby can generate protein isoforms with distinct biological functions.

Alternative Splicing

Around 1980 it was discovered that protein variants of different size can be derived from the same gene. Later, it was shown that these alternative protein products result from differential inclusion of information from a given gene during pre-mRNA splicing. This process, called alternative splicing, entails that pre-mRNA transcripts containing multiple exons can be spliced into different mRNAs and thus encode different proteins with distinct functions. A major consequence of alternative splicing is that the number of proteins in metazoan organisms greatly exceeds the number of genes. Alternative splicing allows differential regulation of gene expression depending on tissue, developmental stage, gender, or external stimuli (Nilsen and Graveley 2010). From genome-wide...

This is a preview of subscription content, log in to check access.

References

  1. Blencowe BJ (2006) Alternative splicing: new insights from global analyses. Cell 126:37–47CrossRefGoogle Scholar
  2. Bonnal S, Martinez C, Forch P, Bachi A, Wilm M, Valcarcel J (2008) RBM5/Luca-15/H37 regulates Fas alternative splice site pairing after exon definition. Mol Cell 32:81–95CrossRefGoogle Scholar
  3. Cavanagh JFW, Palmer IIIAG, Rance M, Skelton NJ (2007) Protein NMR spectroscopy: principles and practice. Academic, LondonGoogle Scholar
  4. Corsini L, Bonnal S, Basquin J, Hothorn M, Scheffzek K, Valcarcel J, Sattler M (2007) U2AF-homology motif interactions are required for alternative splicing regulation by SPF45. Nat Struct Mol Biol 14:620–629CrossRefGoogle Scholar
  5. Gobl C, Madl T, Simon B, Sattler M (2014) NMR approaches for structural analysis of multidomain proteins and complexes in solution. Prog Nucl Magn Reson Spectrosc 80:26–63CrossRefGoogle Scholar
  6. Izquierdo JM, Majos N, Bonnal S, Martinez C, Castelo R, Guigo R, Bilbao D, Valcarcel J (2005) Regulation of Fas alternative splicing by antagonistic effects of TIA-1 and PTB on exon definition. Mol Cell 19:475–484CrossRefGoogle Scholar
  7. Leung AK, Nagai K, Li J (2011) Structure of the spliceosomal U4 snRNP core domain and its implication for snRNP biogenesis. Nature 473:536–539CrossRefGoogle Scholar
  8. Lunde BM, Moore C, Varani G (2007) RNA-binding proteins: modular design for efficient function. Nat Rev Mol Cell Biol 8:479–490CrossRefGoogle Scholar
  9. Mackereth CD, Sattler M (2012) Dynamics in multi-domain protein recognition of RNA. Curr Opin Struct Biol 22:287–296CrossRefGoogle Scholar
  10. Mackereth CD, Simon B, Sattler M (2005) Extending the size of protein-RNA complexes studied by nuclear magnetic resonance spectroscopy. Chembiochem 6:1578–1584CrossRefGoogle Scholar
  11. Mackereth CD, Madl T, Bonnal S, Simon B, Zanier K, Gasch A, Rybin V, Valcarcel J, Sattler M (2011) Multi-domain conformational selection underlies pre-mRNA splicing regulation by U2AF. Nature 475:408–411CrossRefGoogle Scholar
  12. Madl T, Gabel F, Sattler M (2011) NMR and small-angle scattering-based structural analysis of protein complexes in solution. J Struct Biol 173:472–482CrossRefGoogle Scholar
  13. Mourao A, Bonnal S, Soni K, Warner L, Bordonne R, Valcarcel J, Sattler M (2016) Structural basis for the recognition of spliceosomal SmN/B/B′ proteins by the RBM5 OCRE domain in splicing regulation. elife 5:e14707Google Scholar
  14. Nilsen TW, Graveley BR (2010) Expansion of the eukaryotic proteome by alternative splicing. Nature 463:457–463CrossRefGoogle Scholar
  15. Oberstrass FC, Auweter SD, Erat M, Hargous Y, Henning A, Wenter P, Reymond L, Amir-Ahmady B, Pitsch S, Black DL et al (2005) Structure of PTB bound to RNA: specific binding and implications for splicing regulation. Science 309:2054–2057CrossRefGoogle Scholar
  16. Tripsianes K, Madl T, Machyna M, Fessas D, Englbrecht C, Fischer U, Neugebauer KM, Sattler M (2011) Structural basis for dimethylarginine recognition by the Tudor domains of human SMN and SPF30 proteins. Nat Struct Mol Biol 18:1414–1420CrossRefGoogle Scholar
  17. Velazquez-Campoy A, Ohtaka H, Nezami A, Muzammil S, Freire E (2004) Isothermal titration calorimetry. Curr Protoc Cell Biol, Chapter 17: Unit 17 18Google Scholar
  18. Voith von Voithenberg L, Sanchez-Rico C, Kang HS, Madl T, Zanier K, Barth A, Warner LR, Sattler M, Lamb DC (2016) Recognition of the 3′ splice site RNA by the U2AF heterodimer involves a dynamic population shift. Proc Natl Acad Sci USA 113:E7169–E7175CrossRefGoogle Scholar

Copyright information

© European Biophysical Societies' Association (EBSA) 2019

Authors and Affiliations

  1. 1.Institute of Structural BiologyHelmholtz Zentrum MünchenNeuherbergGermany
  2. 2.Biomolecular NMR and Center for Integrated Protein Science Munich, Department ChemieTU MünchenGarchingGermany