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.
Highlights
Splicing of mRNA precursors is an essential part of regulated gene expression
Evidence indicates that splicing has evolved during eukaryogenesis from self-splicing group II introns of prokaryotes together with the spliceosome acting in trans, to catalyze the splicing reaction [1,2]
S. pombe represents an evolutionary intermediate between the constitutive mechanism of splicing in S. cerevisiae and the dynamically regulated process of splicing in humans, which allows alternative splicing of the same pre-mRNA into different mRNAs
Summary
The process consists in the excision of the introns (non-coding sequences) from the precursor mRNA (pre-mRNA), and results in the ligation of the coding sequences (exons), forming the mature mRNA This is achieved by two consecutive trans-esterification reactions, which need to occur at nucleotide precision to avoid frame shifting with adverse consequences on the protein coding potential of the mRNA. The core mechanism of U2-type splicing is conserved from yeast to higher eukaryotes, as is the spliceosome [3]. We will focus on the major spliceosome and U2-type introns and compare introns and the splicing machinery between S. cerevisae, S. pombe, and humans to highlight common ancestor mechanisms and how their increase in complexity over evolution might enable the transition from constitutive to regulated and alternative splicing
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