Origins and Evolution of Spliceosomal Introns

Rodrı́guez-Trelles, Francisco; Tarrı́o, Rosa; Ayala, Francisco J.

doi:10.1146/annurev.genet.40.110405.090625

Cited by 189 publications

(131 citation statements)

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“…It is not known when pre-mRNA splicing developed relative to the fixing of the genetic code, but several arguments favor its presence early in evolution (37,38). We can redirect a modern spliceosome to an incorrect site.…”

Section: Discussionmentioning

confidence: 99%

Exon sequences at the splice junctions affect splicing fidelity and alternative splicing

Crotti

Horowitz²

2009

Proc. Natl. Acad. Sci. U.S.A.

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Identification of splice sites is essential for the expression of most eukaryotic genes, allowing accurate splicing of pre-mRNAs. The splice sites are recognized by the splicing machinery based on sequences within the pre-mRNA. Here, we show that the exon sequences at the splice junctions play a significant, previously unrecognized role in the selection of 3 splice sites during the second step of splicing. The influence of the exon sequences was enhanced by the Prp18 mutant Prp18⌬CR, and the strength of an exon sequence in Prp18⌬CR splicing predicted its effect in wild-type splicing. Analysis of the kinetics of splicing in vitro demonstrated that 3 splice sites were chosen competitively during the second step, likely at the same time as exon ligation. In wild-type yeast, splice site selection for two genes studied was altered by point mutations in their exon bases, affecting splicing fidelity and alternative splicing. Finally, we note that the degeneracy of the genetic code allows competing 3 splice sites to be eliminated from coding regions, and we suggest that the evolution of the splicing signals and the genetic code are connected.pre-mRNA splicing ͉ Prp18 ͉ splice site selection I dentification of splice sites is necessary both for ensuring the fidelity of pre-mRNA splicing and for the regulation of alternative splicing. Mutations that impair the recognition of the splice sites are responsible for a significant fraction of genetic diseases (1). Splice sites are defined by sequence elements in the pre-mRNA that are recognized by many splicing factors (2). The 3Ј splice site is usually the first AG downstream of the branchpoint and is immediately preceded by a pyrimidine or an A (3, 4). A polypyrimidine tract is often present upstream of the splice site. The influence of each element varies and not all are required (5). Recognition of elements in the 3Ј splice site region is required early in splicing in metazoans but not in yeast (6).Identification of the 3Ј splice site for exon ligation appears to occur in the second step, and these events are well studied in yeast. After the first transesterification, the RNA helicase Prp16 rearranges the spliceosome (7). Prp18, Slu7, and Prp22 join the spliceosome, which then rapidly ligates the exons (8-10). The U2, U5, and U6 snRNAs and the Prp8 protein, which are required for the first step of splicing, also participate directly in the second step (11,12).The 3Ј splice site is identified by various mechanisms. The distance between the branch point and the 3Ј splice site is important, with distant sites dependent on their polypyrimidine tracts (13,14). The G's at the 5Ј and 3Ј ends of the intron interact (13, 15), and base Ϫ3 at the 3Ј site interacts with base ϩ3 at the 5Ј site and the U6 snRNA (16). Prp8 is involved in recognition of both the polypyrimidine tract and the AG dinucleotide at the 3Ј splice site (12, 17). Mutation of Slu7 impairs the use of distant sites (18,19). Analyses of in vivo splicing suggest that the 3Ј splice site recognition events occur during th...

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Section: Discussionmentioning

confidence: 99%

Exon sequences at the splice junctions affect splicing fidelity and alternative splicing

Crotti

Horowitz²

2009

Proc. Natl. Acad. Sci. U.S.A.

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“…The origin and evolution of spliceosomal introns has been the subject of much debate (11,35,36), but given structural equivalences, splicing parallels, and chemical reaction identities, there is little doubt that they evolved from group II introns (37). The mobile and invasive group II introns are proposed to have entered the ancestral eukaryotic lineage with the mitochondrial endosymbiosis.…”

Section: Rna Miscompartmentalization As a Roadblock To Gene Expressionmentioning

confidence: 99%

RNA–RNA interactions and pre-mRNA mislocalization as drivers of group II intron loss from nuclear genomes

Dong

Piazza

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Group II introns are commonly believed to be the progenitors of spliceosomal introns, but they are notably absent from nuclear genomes. Barriers to group II intron function in nuclear genomes therefore beg examination. A previous study showed that nuclear expression of a group II intron in yeast results in nonsensemediated decay and translational repression of mRNA, and that these roadblocks to expression are group II intron-specific. To determine the molecular basis for repression of gene expression, we investigated cellular dynamics of processed group II intron RNAs, from transcription to cellular localization. Our data show pre-mRNA mislocalization to the cytoplasm, where the RNAs are targeted to foci. Furthermore, tenacious mRNA-pre-mRNA interactions, based on intron-exon binding sequences, result in reduced abundance of spliced mRNAs. Nuclear retention of pre-mRNA prevents this interaction and relieves these expression blocks. In addition to providing a mechanistic rationale for group II intronspecific repression, our data support the hypothesis that RNA silencing of the host gene contributed to expulsion of group II introns from nuclear genomes and drove the evolution of spliceosomal introns.intron-mediated nuclear gene silencing | spliceosomal intron evolution G roup II introns that reside in genomes of bacteria, archaea, and eukaryotic organelles are ribozymes that self-splice from pre-mRNA transcripts independent of protein catalysis (1-3). Group II introns are also mobile retroelements that integrate into DNAs via an RNA intermediate (2, 3). Group II intron splicing is usually facilitated in vivo by an intron-encoded protein that acts as a maturase to help form the required secondary and tertiary structures (3). The intron RNA-protein complex is also required for group II intron retromobility. Both splicing and mobility of group II introns require interactions between exon-binding sequences (EBSs) within the intron and intron-binding sequences (IBSs) in the flanking exons of RNA or DNA targets (2, 3).The chemical steps of group II intron splicing are identical to those of nuclear spliceosomal introns (4, 5). There are also similarities of RNA sequences at the splice sites and of RNA structures within the ribozyme and the spliceosome (6-9). Because of these parallels, the catalytic group II introns are believed to be the progenitors of spliceosomal introns (6, 10, 11). It is widely speculated that group II introns entered the eukaryotic lineage with the mitochondrial endosymbiosis, invaded the nucleus, and evolved from RNA catalysts into efficient spliceosomedependent introns. However, group II introns are strikingly absent from modern nuclear genomes (1), which are replete with spliceosomal introns. It is still elusive how the ancestral group II introns might have evolved into spliceosomal introns or how they were expunged from nuclear genomes.As an initial effort to answer these questions, we had probed the fate of group II introns introduced into RNA polymerase II transcripts in Saccharomyces cerevis...

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“…Most researchers agree on the existence of an "RNA-Protein World" stage preceeding the divergence of Eubacteria, Archaea, and Eukarya, in which genetic information was stored in RNA [24,61,140,168,187]. Two competing theories postulate either a last common ancestor (LUCA) of the three domains with a DNA genome [13,109], or a LUCA with an RNA genome [41,55,61,89,133].…”

Section: Origins Of Dna Genomesmentioning

confidence: 99%

Innovation in gene regulation: The case of chromatin computation

Prohaska

Stadler

Krakauer

2010

Journal of Theoretical Biology

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Chromatin regulation is understood to be one of the fundamental modes of gene regulation in eukaryotic cells. We argue that the basic proteins that determine the chromatin architecture constitute an evolutionary ancient layer of transcriptional regulation common to all three domains of life. We explore phylogenetically, sources of innovation in chromatin regulation, focusing on protein domains related to chromatin structure and function, demonstrating a step-wise increase of complexity in chromatin regulation. Building upon the highly conserved use of variants of chromosomal architectural proteins to distinguish chromosomal states, Eukarya secondarily acquired mechanisms for "writing" chemical modifications onto chromatin that constitute persistent signals. The acquisition of reader domains enabled decoding of these complex, signal combinations and a decoupling of the signal from immediate biochemical effects. We show how the coupling of reading and writing, which is most prevalent in crown-group Eukarya, could have converted chromatin into a powerful computational device capable of storing and processing more information than pure cis-regulatory networks.Key words: Chromatin, gene regulation, evolution Summary of Findings and Evolutionary HypothesisGene regulation in extant organisms is a complex adaptive system making use of a diversity of mechanisms to ensure that proteins and complementary macromolecular components are produced and maintained at functional levels in variable environments.In this contribution we focus on one key regulatory subsystem of the cell: chromatin regulation. We argue that chromatin functioned as general regulator of transcription in the primordial nucleus, and that a series of key molecular innovations has significantly expanded the regulatory scope of the cell. In this section we summarize the key empirical results of the paper. Sections 2 through 6 provide the empirical support for these claims. In section 7, we formulate an evolutionary Email addresses: sonja@bioinf.uni-leipzig.de (Sonja J. Prohaska), studla@bioinf.uni-leipzig.de (Peter F. Stadler), krakauer@santafe.edu (David C. Krakauer) hypothesis that seeks to explain our findings in terms of the evolution of proto-genetic regulation. We then interpret this evolutionary sequence in terms of increasing computational power by locating key stages of the evolutionary sequence within a formal model of computation. Since sections 2-6 are primarily concerned with presenting evidence, those interested in the conceptual development of the argument can focus on sections 7 and 8.Two variants of Chromosomal Architectural Proteins (ChAPs) are sufficient to define binary genomic, and potentially phenotypic, states. We show how extensions to this binary system lead to potential distinctions among an increasing number of genomic states, culminating in forms of control localized to specific sites in the genome, as illustrated for example by extant mammalian histone variants capable of differential expression and/or localization to r...

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Origins and Evolution of Spliceosomal Introns

Cited by 189 publications

References 251 publications

Exon sequences at the splice junctions affect splicing fidelity and alternative splicing

Exon sequences at the splice junctions affect splicing fidelity and alternative splicing

RNA–RNA interactions and pre-mRNA mislocalization as drivers of group II intron loss from nuclear genomes

Innovation in gene regulation: The case of chromatin computation

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