SufB intein of
            <i>Mycobacterium tuberculosis</i>
            as a sensor for oxidative and nitrosative stresses

Topilina, Natalya I.; Green, Cathleen M.; Jayachandran, Pradeepa; Kelley, Danielle S.; Stanger, Matthew; Piazza, Carol Lyn; Nayak, Sasmita; Belfort, Marlene

doi:10.1073/pnas.1512777112

Cited by 56 publications

(83 citation statements)

References 46 publications

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“…Our findings show that under conditions that include occasional growth of the population, the high fitness cost of the intein guarantees the survival of alleles with the empty target site, even in the absence of inteins without HEN activity. Although here we showed a fitness cost for the intein, several reports have indicated a potential positive role for intein presence, claiming a regulatory function under stress conditions (36)(37)(38)(39)(40). However, our finding that natural H. volcanii populations in the same sampling location tend to be mixed, having both inteinpositive and intein-negative strains sharing the same niche, does not support a strong selective pressure for intein retention in this case.…”

Section: Discussioncontrasting

confidence: 89%

Impact of a homing intein on recombination frequency and organismal fitness

Naor

Altman-Price

Soucy

et al. 2016

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

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Inteins are parasitic genetic elements that excise themselves at the protein level by self-splicing, allowing the formation of functional, nondisrupted proteins. Many inteins contain a homing endonuclease (HEN) domain and rely on its activity for horizontal propagation. However, successful invasion of an entire population will make this activity redundant, and the HEN domain is expected to degenerate quickly under these conditions. Several theories have been proposed for the continued existence of the both active HEN and noninvaded alleles within a population. However, to date, these models were not directly tested experimentally. Using the natural cell fusion ability of the halophilic archaeon Haloferax volcanii we were able to examine this question in vivo, by mating polB intein-positive [insertion site c in the gene encoding DNA polymerase B (polB-c)] and intein-negative cells and examining the dispersal efficiency of this intein in a natural, polyploid population. Through competition between otherwise isogenic intein-positive and intein-negative strains we determined a surprisingly high fitness cost of over 7% for the polB-c intein. Our laboratory culture experiments and samples taken from Israel's Mediterranean coastline show that the polB-c inteins do not efficiently take over an inteinless population through mating, even under ideal conditions. The presence of the HEN/intein promoted recombination when intein-positive and intein-negative cells were mated. Increased recombination due to HEN activity contributes not only to intein dissemination but also to variation at the population level because recombination tracts during repair extend substantially from the homing site. . HENs contribute to the horizontal transmission of these selfish elements into intronless or inteinless alleles, by cleaving the vacant allele to induce homologous recombination or reverse transcription, where the allele containing the intron or intein serves as template. Thus, the intein or intron effectively invades the vacant site and can later be passed on to daughter cells vertically.Paradoxically, if a HEN is highly successful in invading cells, it will saturate all target cells, and then its activity will no longer be under purifying selection. This may result in degeneration of the HEN domain due to accumulation of mutations and will prevent the future horizontal propagation of the intein in question. This phenomenon has been observed in group I introns of bacteriophages (7, 8), eukaryotes (9), and archaea (10). However, active HENs are often observed, and in most natural populations surveyed to date, there are in fact strains with inteins (or introns) containing degenerate HENs, whereas other isolates maintain a fully intact HEN (9). The homing cycle model (11, 12) resolves this paradox by hypothesizing that after the intein-/intron-containing allele has been fixed in the population and after the HEN has completely decayed due to the lack of selection for function of HEN activity, the splicing element (either intron or intein) ...

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Section: Discussioncontrasting

confidence: 89%

Impact of a homing intein on recombination frequency and organismal fitness

Naor

Altman-Price

Soucy

et al. 2016

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

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“…Splicing has the potential to generate irreversible offpathway reactions, the products of which currently have no known function (Topilina et al 2015a). For example, when N-terminal cleavage occurs, the reaction produces free N-extein and intein joined to C-extein (I-C), with less ligated extein (LE); namely, functional RadA.…”

Section: Resultsmentioning

confidence: 99%

Protein splicing of a recombinase intein induced by ssDNA and DNA damage

2016

Self Cite

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Inteins (or protein introns) autocatalytically excise themselves through protein splicing. We challenge the longconsidered notion that inteins are merely molecular parasites and posit that some inteins evolved to regulate host protein function. Here we show substrate-induced and DNA damage-induced splicing, in which an archaeal recombinase RadA intein splices dramatically faster and more accurately when provided with ssDNA. This unprecedented example of intein splicing stimulation by the substrate of the invaded host protein provides compelling support in favor of inteins acting as pause buttons to arrest protein function until needed; then, an immediate activity switch is triggered, representing a new form of post-translational control.

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“…S4) when other Fe deficiency symptoms are still mild suggests that SUFB may play a special role in the acclimation to low Fe. SUFB is also unique in its regulation in mycobacteria where SUFB protein activity is regulated via an intein, a self-cleaving peptide sequence inserted into the polypeptide (Huet et al, 2005;Topilina et al, 2015). Furthermore, in apicomplexan parasites, SufB is the only suf component of the apicoplast (plastid) that is encoded within the small apicoplast genome (Lim and McFadden, 2010) that may allow for regulation of SufB in response to local conditions within the organelle.…”

Section: Effects Of Fe Deficiency On Plastid Fe-s Assembly and S Metamentioning

confidence: 99%