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Review
. 2021 Nov 18;22(22):12444.
doi: 10.3390/ijms222212444.

Evolution of the Early Spliceosomal Complex-From Constitutive to Regulated Splicing

Sonia Borao  1 , José Ayté  1 , Stefan Hümmer  1   2
Affiliations
Review

Evolution of the Early Spliceosomal Complex-From Constitutive to Regulated Splicing

Sonia Borao et al. Int J Mol Sci. .

Abstract

Pre-mRNA splicing is a major process in the regulated expression of genes in eukaryotes, and alternative splicing is used to generate different proteins from the same coding gene. Splicing is a catalytic process that removes introns and ligates exons to create the RNA sequence that codifies the final protein. While this is achieved in an autocatalytic process in ancestral group II introns in prokaryotes, the spliceosome has evolved during eukaryogenesis to assist in this process and to finally provide the opportunity for intron-specific splicing. In the early stage of splicing, the RNA 5' and 3' splice sites must be brought within proximity to correctly assemble the active spliceosome and perform the excision and ligation reactions. The assembly of this first complex, termed E-complex, is currently the least understood process. We focused in this review on the formation of the E-complex and compared its composition and function in three different organisms. We highlight the common ancestral mechanisms in S. cerevisiae, S. pombe, and mammals and conclude with a unifying model for intron definition in constitutive and regulated co-transcriptional splicing.

Keywords: 5′ splicing site; E-complex; Prp2; U2AF65; exon–intron junction; fission yeast; spliceosome; splicing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Modes of alternative splicing. (a) Exon skipping. (b) Mutually exclusive exons. (c) Intron retention. (d) Alternative 5′ ss. (e) Alternative 3′ ss. Lines indicate introns; blue bars indicate constitutive exons; green and orange bars indicate alternative spliced exons; dotted arrows indicate splicing events; dotted vertical lines indicate alternative splice sites.
Figure 2
Figure 2
Definition of the exon–intron junctions. (a) Intron definition. (b) Exon definition. Darker blue bars indicate exons; lighter blue bars indicate introns; blue line indicate intron lariat.
Figure 3
Figure 3
snU1-5′ ss interaction. Nucleotide based interactions of snU1 with the 5′ ss (left) and consensus sequence of the 5′ ss (right) in S. cerevisiae, S. pombe, and mammals. Sequence logos were generated by WebLogo (Version 2.8.2) and sequences of the 5′ ss were derived from: S. cerevisiae [13], S. pombe [98], and mammals [99].
Figure 4
Figure 4
The E-complex in S. cerevisae, S. pombe, and human. Cis- and trans-elements within the exon and intron in (a) budding yeast, (b) fission yeast, and (c) humans. Distance between BP and AG dinucleotide is represented by arrows.
Figure 5
Figure 5
Unified model for co-transcriptional assembly of the E-complex. Co-transcriptional splicing where snRNP U1 subunit U1-70k binds RNA Pol II directly, and Prp40 FF domain binds to the RNA Pol II phosphorylated CTD. Prp40 WW domain binds directly to SF1, bridging 5′ ss and 3′ ss.
See this image and copyright information in PMC

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