Spliceosome

Daniel A Pomeranz Krummel, Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
Kiyoshi Nagai, Medical Research Council Laboratory of Molecular Biology, Cambridge, UK

Published online: September 2005

DOI: 10.1038/npg.els.0005323

The removal of introns and the splicing together of the protein-coding regions or exons from precursor messenger RNA (pre-mRNA) transcripts is fundamental to the development and maintenance of human cells. The nuclear process of pre-mRNA splicing is a complex phenomenon catalyzed by the ‘spliceosome’, which comprises more than 100 hundred protein and RNA molecules that come on and off during its assembly and activity.

Keywords: RNA splicing; spliceosome; pre-mRNA transcript; snRNP; introns

Figure 1. Intron/exon structure. (a) A metazoan pre-mRNA transcript showing the three common sequence elements and their sequence: 5¢ splice (donor) site; branchpoint region containing the highly conserved adenosine (large letter); and 3¢ splice (acceptor) site. Exonic regions are shaded. Y: pyrimidine; R: purine; N: pyrimidine or purine. (b) Introns of protein-coding genes may be one of three types: phase 0 (top; codon CAG for glutamine in exon 1); phase 1 (middle; codon AGG for arginine in exons 1 and 2); phase 2 (bottom; codon GGG for glycine in exons 1 and 2).
Figure 2. Stages of assembly of the U snRNPs onto the pre-mRNA transcript to form the spliceosome, which catalyzes intron removal and exon splicing. (a) Recognition of the 5¢ splice site by U1 snRNP and branchpoint sequences by U2 snRNP, which is mediated by base-pairing of the respective snRNAs with these pre-mRNA sequence elements. (b) First trans-esterification reaction is catalyzed by nucleophilic attack of the 2¢-OH of the sugar of the branchpoint adenosine at the 5¢ splice site. (c) Second trans-esterification reaction is catalyzed by nucleophilic attack of the 3¢-OH of the 5¢ splice site at the 3¢ splice site – a step that is assisted by a loop in U5 snRNA. (d) The 5¢ and 3¢ exons are ligated to form a canonical 3¢–5¢ phosphodiester linkage, and the intron is liberated as a lariat-like structure.
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 References
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    book Burge C, Tuschl T and Sharp PA (1999) "Splicing of precursors to mRNAs by the spliceosomes". In: Gesteland R, Cech T and Atkins J (eds.) RNA World II, pp. 525–560. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
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    book Rymond BC and Rosbash M (1992) "Yeast pre-mRNA splicing". In: Broach JR, Pringle J and Jones EW (eds.) The Molecular and Cellular Biology of the Yeast Saccharomyces, vol. 2, p. 143. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
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 Further Reading
    Berget SM, Moore C and Sharp PA (1977) Spliced segments at the 5¢ terminus of adenovirus 2 late mRNA. Proceedings of the National Academy of Sciences of the United States of America 74: 3171–3175.
    Burd CG and Dreyfuss G (1994) Conserved structures and diversity of functions of RNA-binding proteins. Science 265: 615–621.
    Chow LT, Gelinas RE, Broker TR and Roberts RJ (1977) An amazing sequence arrangement at the 5¢ ends of adenovirus 2 messenger RNA. Cell 12: 1–8.
    Kramer A (1996) The structure and function of proteins involved in mammalian pre-mRNA splicing. Annual Review of Biochemistry 65: 367–409.
    Lamm GM and Lamond AI (1993) Non-snRNP protein splicing factors. Biochimica Biophysica Acta 1173: 247–265.
    Mermoud JE, Cohen PT and Lamond AI (1994) Regulation of mammalian spliceosome assembly by a protein phosphorylation mechanism. EMBO Journal 13: 5679–5688.
    Mount SM (2000) Genomic sequence, splicing, and gene annotation. American Journal of Human Genetics 67: 788–792.
    Oubridge C, Ito N, Evans PR, Teo CH and Nagai K (1994) Crystal structure at 1.92 Å resolution of the RNA-binding domain of the U1A spliceosomal protein complexed with an RNA hairpin. Nature 372: 432–438.
    Reed R (2000) Mechanisms of fidelity in pre-mRNA splicing. Current Opinion in Cell Biology 12: 340–345.
    Sharp PA (1994) Split genes and RNA splicing (Nobel lecture). Cell 77: 805–815.
    Sleeman JE and Lamond AI (1999) Nuclear organization of pre-mRNA splicing factors. Current Opinion in Cell Biology 11: 372–377.
    Varani G and Nagai K (1998) RNA processing by RNP proteins during RNA processing. Annual Review of Biophysics and Biomolecular Structure 27: 407–445.
 Web Links
    ePath Proteome Bioknowledge™ Library http://www.proteome.com

Related Sub-Topics:

Basic Cell Biology, Protein, RNA and DNA | Cell Compartments and Cellular Organelles | RNA Structure and Function | Posttranscriptional Modification | Biomolecular Interactions | Proteins: Structure, Function, Metabolism | Nucleic Acids: Structure, Function, Metabolism
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Article Title: Spliceosome
 
How to Cite close
Pomeranz Krummel, Daniel A, and Nagai, Kiyoshi(Sep 2005) Spliceosome. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005323]