Abstract
Splicing of short introns by the nuclear pre-mRNA splicing machinery is thought to proceed via an "intron definition" mechanism, in which the 5' and 3' splice sites (5'ss, 3'ss, respectively) are initially recognized and paired across the intron. Here, we describe a computational analysis of sequence features involved in recognition of short introns by using available transcript data from five eukaryotes with complete or nearly complete genomic sequences. The information content of five different transcript features was measured by using methods from information theory, and Monte Carlo simulations were used to determine the amount of information required for accurate recognition of short introns in each organism. We conclude: (i) that short introns in Drosophila melanogaster and Caenorhabditis elegans contain essentially all of the information for their recognition by the splicing machinery, and computer programs that simulate splicing specificity can predict the exact boundaries of approximately 95% of short introns in both organisms; (ii) that in yeast, the 5'ss, branch signal, and 3'ss can accurately identify intron locations but do not precisely determine the location of 3' cleavage in every intron; and (iii) that the 5'ss, branch signal, and 3'ss are not sufficient to accurately identify short introns in plant and human transcripts, but that specific subsets of candidate intronic enhancer motifs can be identified in both human and Arabidopsis that contribute dramatically to the accuracy of splicing simulators.
MeSH Terms
3' Untranslated Regions/genetics
5' Untranslated Regions/genetics
Animals
Arabidopsis/genetics
Base Sequence
Binding Sites
Caenorhabditis elegans/genetics
Computational Biology/methods
Drosophila melanogaster/genetics
Humans
Introns/genetics
Monte Carlo Method
RNA Precursors/genetics
RNA Splicing
Saccharomyces cerevisiae/genetics
Software
Transcription, Genetic
Chemicals
3' Untranslated Regions
5' Untranslated Regions
RNA Precursors
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Lim L P
Department of Biology and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Burge C B
References (26)
26 references, click to expand
-
Features of spliceosome evolution and function inferred from an analysis of the information at human splice sites.
J Mol Biol. 1992 Dec 20;228(4):1124-36
PMID: 1474582
-
Splicing signals in Drosophila: intron size, information content, and consensus sequences.
Nucleic Acids Res. 1992 Aug 25;20(16):4255-62
PMID: 1508718
-
AU-rich intronic elements affect pre-mRNA 5' splice site selection in Drosophila melanogaster.
Mol Cell Biol. 1993 Dec;13(12):7689-97
PMID: 8246985
-
Intron definition in splicing of small Drosophila introns.
Mol Cell Biol. 1994 May;14(5):3434-45
PMID: 8164690
-
Exon recognition in vertebrate splicing.
J Biol Chem. 1995 Feb 10;270(6):2411-4
PMID: 7852296
-
Localization of sequences required for size-specific splicing of a small Drosophila intron in vitro.
J Mol Biol. 1995 Oct 27;253(3):426-37
PMID: 7473725
-
An intron splicing enhancer containing a G-rich repeat facilitates inclusion of a vertebrate micro-exon.
RNA. 1996 Apr;2(4):342-53
PMID: 8634915
-
Functional analysis of an intron 3' splice site in Caenorhabditis elegans.
RNA. 1996 Apr;2(4):380-8
PMID: 8634918
-
Intramolecular structure in yeast introns aids the early steps of in vitro spliceosome assembly.
RNA. 1996 Jun;2(6):509-22
PMID: 8718681
-
Architectural limits on split genes.
Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15081-5
PMID: 8986767
-
Prediction of complete gene structures in human genomic DNA.
J Mol Biol. 1997 Apr 25;268(1):78-94
PMID: 9149143
-
A branch point consensus from Arabidopsis found by non-circular analysis allows for better prediction of acceptor sites.
Nucleic Acids Res. 1997 Aug 1;25(15):3159-63
PMID: 9224618
-
G triplets located throughout a class of small vertebrate introns enforce intron borders and regulate splice site selection.
Mol Cell Biol. 1997 Aug;17(8):4562-71
PMID: 9234714
-
Intron self-complementarity enforces exon inclusion in a yeast pre-mRNA.
Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12467-72
PMID: 9356473
-
Genome-wide bioinformatic and molecular analysis of introns in Saccharomyces cerevisiae.
RNA. 1999 Feb;5(2):221-34
PMID: 10024174
-
Intron size and natural selection.
Nature. 1999 Sep 23;401(6751):344
PMID: 10517631
-
Test of the combinatorial model of intron recognition in a native maize gene.
Plant Mol Biol. 1999 Nov;41(5):637-44
PMID: 10645723
-
Test of intron predictions reveals novel splice sites, alternatively spliced mRNAs and new introns in meiotically regulated genes of yeast.
Nucleic Acids Res. 2000 Apr 15;28(8):1700-6
PMID: 10734188
-
UBP1, a novel hnRNP-like protein that functions at multiple steps of higher plant nuclear pre-mRNA maturation.
EMBO J. 2000 Apr 3;19(7):1638-49
PMID: 10747031
-
From bioinformatics to computational biology.
Genome Res. 2000 Sep;10(9):1277-9
PMID: 10984445
-
An intronic splicing enhancer binds U1 snRNPs to enhance splicing and select 5' splice sites.
Mol Cell Biol. 2000 Dec;20(24):9225-35
PMID: 11094074
-
Initial sequencing and analysis of the human genome.
Nature. 2001 Feb 15;409(6822):860-921
PMID: 11237011
-
Heuristic informational analysis of sequences.
Nucleic Acids Res. 1986 Jan 10;14(1):179-96
PMID: 3753763
-
Introduction of functional artificial introns into the naturally intronless ura4 gene of Schizosaccharomyces pombe.
Mol Cell Biol. 1989 Apr;9(4):1526-35
PMID: 2725514
-
The AU-rich sequences present in the introns of plant nuclear pre-mRNAs are required for splicing.
Cell. 1989 Aug 11;58(3):473-83
PMID: 2758463
-
Detecting subtle sequence signals: a Gibbs sampling strategy for multiple alignment.
Science. 1993 Oct 8;262(5131):208-14
PMID: 8211139