Splice Sites

Splice sites are the sequences that define the junctions between introns and exons in eukaryotic genes.

Keywords: pre-mRNA; RNA processing; splicing; consensus sequences; spliceosome; snRNA; snRNP; splicing enhancer elements

Figure 1. The pre-mRNA splicing reaction and snRNA interactions in the spliceosomes. (a) Diagram of the two-step spliceosomal splicing reaction described in the text. (b) RNA–RNA interactions in the major, U2-dependent spliceosome. (Left) The initial interactions of the pre-mRNA with U1 and U2 snRNPs. (Right) The interactions in the mature spliceosome. Hatched bars indicate regions that interact by base-pairing. The adenosine residue at the branch site is circled. (c) RNA–RNA interactions in the minor, U12-dependent spliceosome.
Figure 2. Pictograms of the major U2-dependent intron class consensus splice site signals. Approximately 20000 5¢ and 3¢ splice sites from annotated GenBank files were extracted and aligned as described in Burge et al. 1999. In these pictograms, the size of a letter corresponds to the frequency with which that base is present at each position in a compilation of splice sites. (a) Major class 5¢ splice site consensus sequence. The position labeled 1 is the first nucleotide of the intron and the position labeled –1 is the last nucleotide of the upstream exon. (b) Major class branch site consensus. A small database of experimentally confirmed branch sites (Nelson and Green, 1989) was used to generate this pictogram. The position labeled 1 is the branch site residue. (c) Major class 3¢ splice site consensus. The position labeled –1 is the last nucleotide of the intron and the position labeled 1 is the first nucleotide of the downstream exon.
Figure 3. Pictograms of the minor U12-dependent intron class consensus splice site signals. Because the consensus sequences differ between the GU–AG and AU–AC subclasses of U12-dependent introns, these are presented separately. The GU–AG subclass consensus was derived from 160 examples, while the AU–AG subclass consensus was derived from 30 examples. (a) Minor class GU 5¢ splice site consensus sequence. The position labeled 1 is the first nucleotide of the intron and the position labeled –1 is the last nucleotide of the upstream exon. (b) Minor class GU–AG branch site consensus sequence. The position labeled 1 is the branch site residue. (c) Minor class AG 3¢ splice site consensus. The position labeled –1 is the last nucleotide of the intron and the position labeled 1 is the first nucleotide of the downstream exon. (d) Minor class AU 5¢ splice site consensus sequence. (e) Minor class AU–AC branch site consensus sequence. (f) Minor class AC 3¢ splice site consensus sequence.
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 References
    book Beggs JD (2001) "Spliceosomal machinery". In: Encyclopedia of Life Sciences, http://www.els.net, London: Nature Publishing Group.
    Blencowe BJ (2000) Exonic splicing enhancers: mechanism of action, diversity and role in human genetic diseases. Trends in Biochemical Science 25: 106–110.
    Burge C and Karlin S (1997) Prediction of complete gene structures in human genomic DNA. Journal of Molecular Biology 268: 78–94.
    Burge CB, Padgett RA and Sharp PA (1998) Evolutionary fates and origins of U12-type introns. Molecular Cell 2: 773–785.
    book Burge CB, Tuschl T and Sharp PA (1999) "Splicing of precursors to mRNAs by the spliceosome". In: Gestland RF, Cech T and Atkins JF (eds.) The RNA World II, pp. 525–560. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
    Dietrich RC, Incoravia R and Padgett RA (1997) Terminal intron dinucleotide sequences do not distinguish between U2- and U12-dependent introns. Molecular Cell 1: 151–160.
    Dietrich RC, Peris MJ, Seyboldt AS and Padgett RA (2001) Role of the 3¢ splice site in U12-dependent intron splicing. Molecular Cell Biology 21: 1942–1952.
    Jackson IJ (1991) A reappraisal of non-consensus mRNA splice sites. Nucleic Acids Research 19: 3795–3798.
    Maroney PA, Romfo CM and Nilsen TW (2000) Functional recognition of 5¢ splice site by U4/U6 • U5 tri-snRNP defines a novel ATP-dependent step in early spliceosome assembly. Molecular Cell 6: 317–328.
    Moore MJ (2000) Intron recognition comes of AGe. Nature Structural Biology 7: 14–16.
    book Newman AJ (2001) "RNA interactions in mRNA splicing". In: Encyclopedia of Life Sciences. London, UK: Nature Publishing Group.
    book Nilsen TW (1998) "RNA–RNA interactions in nuclear pre-mRNA splicing". In: Simons RW and Grunberg-Manago M (eds.) RNA Structure and Function, pp. 279–307. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
    book Padgett RA (2001) "mRNA splicing: role of snRNAs". In: Encyclopedia of Life Sciences. London, UK: Nature Publishing Group.
    Tarn W-Y and Steitz JA (1996) Highly diverged U4 and U6 small nuclear RNAs required for splicing rare AT–AC introns. Science 273: 1824–1832.
 Further Reading
    Lund M and Kjems J (2002) Defining a 5¢ splice site by functional selection in the presence and absence of U1 snRNA 5¢ end. RNA 8: 166–179.
    Tarn W-Y and Steitz JA (1997) Pre-mRNA splicing: the discovery of a new spliceosome doubles the challenge. Trends in Biochemical Sciences 22: 132–137.
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Padgett, Richard A, and Burge, Christopher B(Sep 2005) Splice Sites. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005044]