Fate of the junction phosphate in alternating forward and reverse self-splicing reactions of group II intron RNA

Müller, Manfred; Stocker, Paul; Hetzer, Martin W.; Schweyen, Rudolf J.

doi:10.1016/0022-2836(91)90201-g

Cited by 15 publications

(22 citation statements)

References 22 publications

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“…2f). Remarkably, the active sites of group II introns can accommodate a diversity of nucleophiles (2′-OH group, 3′-OH group and water) and substrates (DNA and RNA) and, in addition to splicing, can catalyse several other reactions, which are either adaptations of the basic splicing activity or distinct reactions such as terminal transferase activity 24 . Somewhat unexpectedly, the group I-like ribozyme GIR1 from the slime mould Didymium iridis forms a 2′,5′-lariat, similar to that of the group II introns 25 (FIG.…”

Section: Splicing Ribozymesmentioning

confidence: 99%

Ribozymes, riboswitches and beyond: regulation of gene expression without proteins

2007

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Although various functions of RNA are carried out in conjunction with proteins, some catalytic RNAs, or ribozymes, which contribute to a range of cellular processes, require little or no assistance from proteins. Furthermore, the discovery of metabolite-sensing riboswitches and other types of RNA sensors has revealed RNA-based mechanisms that cells use to regulate gene expression in response to internal and external changes. Structural studies have shown how these RNAs can carry out a range of functions. In addition, the contribution of ribozymes and riboswitches to gene expression is being revealed as far more widespread than was previously appreciated. These findings have implications for understanding how cellular functions might have evolved from RNA-based origins.More than 40 years of extensive research has revealed that RNAs participate in a range of cellular functions. Some RNAs, despite being composed of only four chemically similar nucleotides, can fold into distinct three-dimensional architectures. In many cases, these constitute simple scaffolds that provide binding sites for proteins that function together with the RNAs. However, the discovery of the first catalytic RNAs -later named RNA enzymes, or ribozymes -in the 1980s demonstrated that RNAs can also have important functional roles in their own right 1,2 . The list of naturally occuring ribozymes is short, and additions over the years have been rare, with each new discovery eliciting considerable excitement in the field.Studies of molecular evolution suggest that RNA molecules significantly influenced the development of modern organisms by mediating the genetic flow from DNA to proteins, as well as through their own contribution to catalytic functions. The 'RNA world' hypothesis implies that RNA molecules appeared before DNA and proteins 3 . Nevertheless, even with a head start, RNA catalysts do not prevail in the modern world. Moreover, most ubiquitous ribozymes require proteins for efficient catalysis in vivo, and most true protein-devoid catalytic RNAs have been found in only a few viral-like sources, suggesting that the contribution of protein-free RNAs to the functions of modern cells has been limited.Correspondence to A.S. or D.J.P. serganoa@mskcc.org; pateld@mskcc.org. Competing interests statementThe authors declare no competing financial interests. HHS Public AccessAuthor manuscript Nat Rev Genet. Author manuscript; available in PMC 2015 December 23. Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptThe discovery of riboswitches 4-6 and other RNA-based sensors reignited interest in the roles of protein-devoid RNA-based elements. These RNA sensors can be broadly defined as mRNA regions that are capable of modulating gene expression in response to internal and external inputs, without the initial participation of proteins. Unlike ribozymes, many of these sensors direct gene expression purely through changes in RNA conformation. For instance, riboswitches alter their conformations in response to small metabolite...

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Section: Splicing Ribozymesmentioning

confidence: 99%

Ribozymes, riboswitches and beyond: regulation of gene expression without proteins

2007

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“…This base pairing interaction renders the phosphorus atom 3' adjacent to the GACAGA motif (GACAGA:pN) in the donor RNA prone to a nucleophilic attack by the 3' oxygen atom of the lariat IVS (intron charging by transesterification). In a similar manner, in the discharging reaction the phosphorus atom that forms the 3' splice site becomes specifically transesterified by the 3' oxygen atom of the GACAGA sequence of the acceptor RNA (20).…”

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confidence: 99%

“…Like group I self-splicing, self-splicing of the mitochondrial Saccharomyces group II phosphorus atom in this charging-discharging pathway (20), is provided by intermolecular base pair interactions (EBS-IBS interaction) (24). The selection involves a minimum of six nucleotides in the substrate (IBS 1: 5'-GACAGA) that are complementary to an intron internal guide sequence, the EBS1 site (5'-UCUGUC).…”

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confidence: 99%

“…As a result, the IBS1 GACAGpA sequence of the donor RNA is dissected and the 3' terminal adenosine residue, together with the 3' exon portion, is transferred to the 3' end of the lariat IVS (20). Interacting cycles of IVS (-1) charging combined with accurate discharging by a GACAGA molecule may enable the bIl lariat to act as a progressive RNA polymerase (nucleotidyl insertase) in an orderly 3'…”

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confidence: 99%

“…The authentic RNA recombination. In a two-step transesterification pathway that involves lariat IVS charging (1) and discharging (2), the 3' portion of a donor RNA becomes transferred to the 3' end of an acceptor molecule (20). (B) Predicted models for catalyzed adenosine insertion (left) and deletion (right) by two successive transesterifications.…”

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Group II Intron RNA Catalysis of Progressive Nucleotide Insertion: a Model for RNA Editing

Mueller

Hetzer

Schweyen

1993

Science

Self Cite

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The self-splicing bl1 intron lariat from mitochondria of Saccharomyces cerevisiae catalyzed the insertion of nucleotidyl monomers derived from the 3' end of a donor RNA into an acceptor RNA in a 3' to 5' direction in vitro. In this catalyzed reaction, the site specificity provided by intermolecular base pair interactions, the formation of chimeric intermediates, the polarity of the nucleotidyl insertion, and its reversibility all resemble such properties in previously proposed models of RNA editing in kinetoplastid mitochondria. These results suggest that RNA editing occurs by way of a concerted, two-step transesterification mechanism and that RNA splicing and RNA editing might be prebiotically related mechanisms; possibly, both evolved from a primordial demand for self-replication.

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Interaction of intronic boundaries is required for the second splicing step efficiency of a group II intron.

Chanfreau

Jacquier²

1993

The EMBO Journal

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Group II and nuclear pre-mRNAs introns share a common splicing pathway involving a lariat intennediate, as well as some primary sequence similarities at the splice junctions.In this work, we analyze the role of the conserved nucleotides at the first and penultimate positions (Gl and A886) of a group II self-splicing intron.We show that the Gi nucleotide is essential for the efficiency of both the first and the second splicing steps, while substitutions at the penultimate nucleotide affect mostly the efficiency of the second step. A reciprocal suppression of the second splicing step defect can be observed in some double mutants. This result is best explained by a non-Watson-Crick interaction between the first and the penultimate nucleotides of the intron, which occurs after lariat formation. The fmding that an interaction between intron boundaries is required for the second splicing step in both group II and nuclear premRNA introns strengthens the idea that both systems employ similar mechanisms, albeit with differences in the details of the nucleotide interactions.

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Fate of the junction phosphate in alternating forward and reverse self-splicing reactions of group II intron RNA

Cited by 15 publications

References 22 publications

Ribozymes, riboswitches and beyond: regulation of gene expression without proteins

Ribozymes, riboswitches and beyond: regulation of gene expression without proteins

Group II Intron RNA Catalysis of Progressive Nucleotide Insertion: a Model for RNA Editing

Interaction of intronic boundaries is required for the second splicing step efficiency of a group II intron.

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