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Review
. 2002;10(1-2):79-92.

RNA-protein interactions that regulate pre-mRNA splicing

Ravinder Singh  1
Affiliations
Review

RNA-protein interactions that regulate pre-mRNA splicing

Ravinder Singh. Gene Expr. 2002.

Abstract

Splicing of nuclear precursor messenger RNAs is an important and ubiquitous type of gene regulation in metazoans. Splicing joins the coding sequences called exons by removing the intervening noncoding sequences, introns, from primary transcripts. Alternative splicing generates an enormous repertoire of functional diversity by producing multiple RNAs and proteins from a single gene. In fact, recent genome sequences from several organisms suggest that splicing regulation is likely to provide an important source of functional diversity in more complex organisms. Because splice sites are short sequences at the ends of introns, the functional splice sites have to be distinguished from an excessively large number of sequences in the primary transcripts that resemble a splice site. Furthermore, alternative splice sites have to be correctly chosen at appropriate times. Thus, selection of proper splice sites remains a daunting biological problem. This review focuses on a few examples in which the molecular and biochemical basis for splice site selection is better understood.

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Figures

Figure 1
Figure 1
Intron splicing signals and their recognition. (A) The 5′ splice site, the branch site, the polypyrimidine tract, and the 3′ splice site consensus sequences are shown for both the U2- and U12-dependent introns. (B) Base pairing interactions between the splicing signals and the U snRNAs for the U2- and U12-dependent introns are shown. (C) Two transesterification reactions. Arrows show step 1 and step 2 of splicing. For clarity, only U snRNPs are shown. A, adenine; G, guanine; C, cytosine; U, uracil; T, thymine; R, adenine or guanine; Y, cytosine or uracil.
Figure 2
Figure 2
Sex determination pathway in Drosophila melanogaster. Only the genes that are known to be relevant for alternative splicing are shown. DSXM and DSXF are the male- and female-specific forms of the DSX protein. Sex-lethal, Sxl; transformer, tra; doublesex, dsx; male-specific lethal 2, msl2; and fruitless, fru.
Figure 3
Figure 3
Role of RNA cis elements in alternative splicing. (A) The early transcripts of the Sxl gene exclude the male-specific exon by default (top). However, late transcripts include this exon by default (bottom). (B) Mutually exclusive exons. Recruitment of U2AF and U2 snRNP blocks the assembly of the spliceosome at the 5′ splice site of exon 2 (top). However, blockage of the 5′ and 3′ splice sites of exon 3 and activation of the 3′ splice site of exon 2 facilitate inclusion of exon 2 (bottom).
Figure 4
Figure 4
Role of trans-acting factors in alternative splicing. (A) Alternative 5′ splice site selection of the SV-40 pre-mRNA by ASF/SF2 and hnRNP A1. (B) 5′ splice site repression of the Drosophila P element intron by a large complex assembled onto the pseudo 5′ splice sites (F1 and F2) in somatic cells. (C) 3′ splice site switching of the tra pre-mRNA. SXL directly competes with U2AF for the NSS polypyrimidine-tract/3′ splice and mediates 3′ splice site switching in females. (D) Exon exclusion by SXL during splicing autoregulation. The binding of SXL to uridine-rich sequences in the flanking introns mediates skipping of the male-specific exon in its own pre-mRNA. (E) 3′ splice site activation of the dsx pre-mRNA by TRA, TRA2, RBP1, and dSF2 proteins, which assemble on the exonic splicing enhancers. The site of polyadenylation for female-specific transcripts is also shown. (F) Intron retention in msl2 by SXL, which is a negative regulator. Removal of this intron in males requires TIA-1, which is a positive regulator. Alternative splicing patterns are shown by thin lines below and above the transcripts. The names of the genes are indicated below the transcripts on the left. Boxes, exons; horizontal lines, introns; STOP, translation termination codon.
Figure 5
Figure 5
Exon definition. For internal exons, initial recognition of the splice sites may be facilitated by interactions among splicing factors either (a) across exons or (b) across intron. For terminal exons, initial recognition of the splice sites may involve interactions with either (c) the cap binding complex at the 5′ end or (d) the polyadenylation machinery at the 3′ end. The vertical bars within box are splicing enhancers. Circles and ovals are snRNPs, splicing factors/activators, cap binding complex, or polyadenylation machinery.
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References

    1. Adams M. D.; Celniker S. E.; Holt R. A.; et al. The genome sequence of Drosophila melanogaster . Science 287:2185–2195; 2000. - PubMed
    1. Ashiya M.; Grabowski P. J. A neuron-specific splicing switch mediated by an array of pre-mRNA repressor sites: Evidence of a regulatory role for the polypyrimidine tract binding protein and a brain-specific PTB counterpart. RNA 3:996–1015; 1997. - PMC - PubMed
    1. Bashaw G. J.; Baker B. S. The regulation of the Drosophila msi-2 gene reveals a function for Sex-lethal in translational control. Cell 89:789–798; 1997. - PubMed
    1. Berget S. M. Exon recognition in vertebrate splicing. J. Biol. Chem. 270:2411–2414; 1995. - PubMed
    1. Black D. L. Protein diversity from alternative splicing: A challenge for bioinformatics and post-genome biology. Cell 103:367–370; 2000. - PubMed

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