Splice Sites

Abstract

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.. 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

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.

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.

Newman AJ (2001) RNA interactions in mRNA splicing. In: Encyclopedia of Life Sciences. London, UK: Nature Publishing Group.

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.

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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How to Cite close
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]