Alternate Splicing
Alternative splicing: current perspectives
Eddo Kim,{ Amir Goren,{ and Gil Ast*
Summary
Alternativesplicingisawell-characterizedmechanismby which multiple transcripts are generated from a single mRNA precursor. By allowing production of several proteinisoformsfromonepre-mRNA,alternativesplicing contributes to proteomic diversity. But what do we know about the origin of this mechanism? Do the same evolutionary forces apply to alternatively and constitutively splice exons? Do similar forces act on all types of alternative splicing? Are the products generated by alternative splicing functional? Why is ‘‘improper’’ recognition of exons and introns allowed by the splicing machinery? In this review, we summarize the current knowledge regarding these issues from an evolutionary perspective. BioEssays 30:38–47, 2008. 2007 Wiley Periodicals, Inc.
Introduction
Splicing is the process by which introns are removed from an mRNA precursor (pre-mRNA) and exons are ligated to form a mature mRNA.(1) Most types of splicing, in organisms ranging from yeast to human, take place within the spliceosome—a large complex composed of five ribonucleoproteins (RNPs) containing the small nuclear RNAs (snRNAs) U1, U2, U4, U5 and U6 and as many as 150 proteins.(2–5) The splicing machinery recognizes exons and introns by using multiple signals, which presumably results in a network of interactions across exons and/or introns; this recognition is known as exon definition and intron definition, respectively.(6) The four main splice signals that delineate the proper exon–intron boundaries are (1) the 50 and (2) the 30 splice sites (50ss and 30ss), located at the upstream and downstream exon–intron junctions, respectively, (3) the branch site (BS), and (4) the polypyrimidine tract, which is located upstream of the 30ss(1,7) (Fig. 1A).
In metazoans, these four splice signals are not sufficient for the recognition of exons and introns by the splicing machinery; it has beenestimated
Eddo Kim,{ Amir Goren,{ and Gil Ast*
Summary
Alternativesplicingisawell-characterizedmechanismby which multiple transcripts are generated from a single mRNA precursor. By allowing production of several proteinisoformsfromonepre-mRNA,alternativesplicing contributes to proteomic diversity. But what do we know about the origin of this mechanism? Do the same evolutionary forces apply to alternatively and constitutively splice exons? Do similar forces act on all types of alternative splicing? Are the products generated by alternative splicing functional? Why is ‘‘improper’’ recognition of exons and introns allowed by the splicing machinery? In this review, we summarize the current knowledge regarding these issues from an evolutionary perspective. BioEssays 30:38–47, 2008. 2007 Wiley Periodicals, Inc.
Introduction
Splicing is the process by which introns are removed from an mRNA precursor (pre-mRNA) and exons are ligated to form a mature mRNA.(1) Most types of splicing, in organisms ranging from yeast to human, take place within the spliceosome—a large complex composed of five ribonucleoproteins (RNPs) containing the small nuclear RNAs (snRNAs) U1, U2, U4, U5 and U6 and as many as 150 proteins.(2–5) The splicing machinery recognizes exons and introns by using multiple signals, which presumably results in a network of interactions across exons and/or introns; this recognition is known as exon definition and intron definition, respectively.(6) The four main splice signals that delineate the proper exon–intron boundaries are (1) the 50 and (2) the 30 splice sites (50ss and 30ss), located at the upstream and downstream exon–intron junctions, respectively, (3) the branch site (BS), and (4) the polypyrimidine tract, which is located upstream of the 30ss(1,7) (Fig. 1A).
In metazoans, these four splice signals are not sufficient for the recognition of exons and introns by the splicing machinery; it has beenestimated