Global Regulators Orchestrate Group II Intron Retromobility

Coros, Colin J.; Piazza, Carol Lyn; Chalamcharla, Venkata R.; Smith, Dorie; Belfort, Marlene

doi:10.1016/j.molcel.2009.03.014

Cited by 45 publications

(47 citation statements)

References 33 publications

(43 reference statements)

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“…These processes promote base-substitutions (56,58), frame-shift mutations (40), amplification (40), mobileintron movement (57), and transposon excision (49,57). These examples illustrate the apparently multiple evolutions of mechanisms that couple genomic instability pathways with stress responses and stress.…”

Section: Dsb-dependent Stress-induced Mutagenesis In Wild-type Strainmentioning

confidence: 99%

Impact of a stress-inducible switch to mutagenic repair of DNA breaks on mutation in Escherichia coli

Shee

Gibson

Darrow

et al. 2011

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

122

259

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Basic ideas about the constancy and randomness of mutagenesis that drives evolution were challenged by the discovery of mutation pathways activated by stress responses. These pathways could promote evolution specifically when cells are maladapted to their environment (i.e., are stressed). However, the clearest example-a general stress-response-controlled switch to errorprone DNA break (double-strand break, DSB) repair-was suggested to be peculiar to an Escherichia coli F′ conjugative plasmid, not generally significant, and to occur by an alternative stress-independent mechanism. Moreover, mechanisms of spontaneous mutation in E. coli remain obscure. First, we demonstrate that this same mechanism occurs in chromosomes of starving F − E. coli. I-SceI endonuclease-induced chromosomal DSBs increase mutation 50-fold, dependent upon general/starvation-and DNA-damage-stress responses, DinB error-prone DNA polymerase, and DSB-repair proteins. Second, DSB repair is also mutagenic if the RpoS generalstress-response activator is expressed in unstressed cells, illustrating a stress-response-controlled switch to mutagenic repair. Third, DSB survival is not improved by RpoS or DinB, indicating that mutagenesis is not an inescapable byproduct of repair. Importantly, fourth, fully half of spontaneous frame-shift and base-substitution mutation during starvation also requires the same stress-response, DSB-repair, and DinB proteins. These data indicate that DSB-repairdependent stress-induced mutation, driven by spontaneous DNA breaks, is a pathway that cells usually use and a major source of spontaneous mutation. These data also rule out major alternative models for the mechanism. Mechanisms that couple mutagenesis to stress responses can allow cells to evolve rapidly and responsively to their environment.antibiotic resistance | cancer | genome evolution | rapid evolution | stressinduced mutagenesis H ow, when, and where mutations form underpins understanding pathogen-host interactions, antibiotic resistance, aging, cancer progression and therapy resistance, and evolution generally. Initial models of mutagenesis that drives evolution imagined random stochastic processes, roughly constant with time, and blind to selective environments (1). In contrast, bacterial, yeast, and human cells appear to possess mechanisms that induce mutation pathways specifically during stress, under the control of stress responses (2) (stress-induced mutagenesis or SIM). These pathways suggest mechanisms by which genetic diversity could be generated preferentially when cells are maladapted to their environment (i.e., are stressed), potentially accelerating evolution responsively to environments, a major departure from classic views (1). However, the significance of such mechanisms has been debated, as have the mechanisms themselves.First, mutagenesis associated with the DNA-damage response has been argued to be an unavoidable consequence of induced DNA repair (3, 4), not an evolutionary engine (5, 6). Second, the strongest support for the idea of increas...

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Section: Dsb-dependent Stress-induced Mutagenesis In Wild-type Strainmentioning

confidence: 99%

Impact of a stress-inducible switch to mutagenic repair of DNA breaks on mutation in Escherichia coli

Shee

Gibson

Darrow

et al. 2011

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

122

259

View full text Add to dashboard Cite

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“…As expected, pathways using nascent DNA strands as primers are favored under rapid growth conditions, which lead to an increased frequency of replication forks (Coros et al 2005). Retromobility of the Ll.LtrB intron is also influenced in interesting ways by cellular interactions, host factors, and stress responses (Beauregard et al 2008;Zhao et al 2008;Coros et al 2009). …”

Section: Group II Intronsmentioning

confidence: 99%

Group II Introns: Mobile Ribozymes that Invade DNA

Lambowitz

Zimmerly

2010

Cold Spring Harbor Perspectives in Biology

387

526

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SUMMARYGroup II introns are mobile ribozymes that self-splice from precursor RNAs to yield excised intron lariat RNAs, which then invade new genomic DNA sites by reverse splicing. The introns encode a reverse transcriptase that stabilizes the catalytically active RNA structure for forward and reverse splicing, and afterwards converts the integrated intron RNA back into DNA. The characteristics of group II introns suggest that they or their close relatives were evolutionary ancestors of spliceosomal introns, the spliceosome, and retrotransposons in eukaryotes. Further, their ribozyme-based DNA integration mechanism enabled the development of group II introns into gene targeting vectors ("targetrons"), which have the unique feature of readily programmable DNA target specificity.

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“…Data suggest that group II intron mobility depends on host genes and cellular factors and that group II intron activity may be coordinated with physiological processes that are of critical importance to the cell (Coros et al 2008(Coros et al , 2009Yao et al 2013). However, given that most of our understanding of the RNP comes from in vitro self-assembly experiments and from genetic analyses, the potentially complex nature of the relationship of the intron RNP with its molecular environment remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Group II intron–ribosome association protects intron RNA from degradation

Contreras

Huang

Piazza

et al. 2013

RNA

Self Cite

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The influence of the cellular environment on the structures and properties of catalytic RNAs is not well understood, despite great interest in ribozyme function. Here we report on ribosome association of group II introns, which are ribozymes that are important because of their putative ancestry to spliceosomal introns and retrotransposons, their retromobility via an RNA intermediate, and their application as gene delivery agents. We show that group II intron RNA, in complex with the intron-encoded protein from the native Lactoccocus lactis host, associates strongly with ribosomes in vivo. Ribosomes have little effect on intron ribozyme activities; rather, the association with host ribosomes protects the intron RNA against degradation by RNase E, an enzyme previously shown to be a silencer of retromobility in Escherichia coli. The ribosome interacts strongly with the intron, exerting protective effects in vivo and in vitro, as demonstrated by genetic and biochemical experiments. These results are consistent with the ribosome influencing the integrity of catalytic RNAs in bacteria in the face of degradative nucleases that regulate intron mobility.

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Global Regulators Orchestrate Group II Intron Retromobility

Cited by 45 publications

References 33 publications

Impact of a stress-inducible switch to mutagenic repair of DNA breaks on mutation in Escherichia coli

Impact of a stress-inducible switch to mutagenic repair of DNA breaks on mutation in Escherichia coli

Group II Introns: Mobile Ribozymes that Invade DNA

Group II intron–ribosome association protects intron RNA from degradation

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