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dc.contributor.author
Martini, María Carla
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dc.contributor.author
Hicks, Nathan D.
dc.contributor.author
Xiao, Junpei
dc.contributor.author
Alonso, Maria Natalia
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dc.contributor.author
Barbier, Thibault
dc.contributor.author
Sixsmith, Jaimie
dc.contributor.author
Fortune, Sarah M.
dc.contributor.author
Shell, Scarlet S.
dc.date.available
2023-09-25T19:05:51Z
dc.date.issued
2022-07
dc.identifier.citation
Martini, María Carla; Hicks, Nathan D.; Xiao, Junpei; Alonso, Maria Natalia; Barbier, Thibault; et al.; Loss of RNase J leads to multi-drug tolerance and accumulation of highly structured mRNA fragments in Mycobacterium tuberculosis; Public Library of Science; Plos Pathogens; 18; 7; 7-2022; 1-22
dc.identifier.issn
1553-7366
dc.identifier.uri
http://hdl.handle.net/11336/212976
dc.description.abstract
Despite the existence of well-characterized, canonical mutations that confer high-level drug resistance to Mycobacterium tuberculosis (Mtb), there is evidence that drug resistance mechanisms are more complex than simple acquisition of such mutations. Recent studies have shown that Mtb can acquire non-canonical resistance-associated mutations that confer survival advantages in the presence of certain drugs, likely acting as stepping-stones for acquisition of high-level resistance. Rv2752c/rnj, encoding RNase J, is disproportionately mutated in drug-resistant clinical Mtb isolates. Here we show that deletion of rnj confers increased tolerance to lethal concentrations of several drugs. RNAseq revealed that RNase J affects expression of a subset of genes enriched for PE/PPE genes and stable RNAs and is key for proper 23S rRNA maturation. Gene expression differences implicated two sRNAs and ppe50-ppe51 as important contributors to the drug tolerance phenotype. In addition, we found that in the absence of RNase J, many short RNA fragments accumulate because they are degraded at slower rates. We show that the accumulated transcript fragments are targets of RNase J and are characterized by strong secondary structure and high G+C content, indicating that RNase J has a rate-limiting role in degradation of highly structured RNAs. Taken together, our results demonstrate that RNase J indirectly affects drug tolerance, as well as reveal the endogenous roles of RNase J in mycobacterial RNA metabolism.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Public Library of Science
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
MYCOBACTERIUM TUBERCULOSIS
dc.subject
RNASE J
dc.subject
ANTIBIOTIC RESISTANCE
dc.subject
RNA METABOLISM
dc.subject.classification
Bioquímica y Biología Molecular
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Loss of RNase J leads to multi-drug tolerance and accumulation of highly structured mRNA fragments in Mycobacterium tuberculosis
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2023-07-04T10:54:42Z
dc.journal.volume
18
dc.journal.number
7
dc.journal.pagination
1-22
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
San Francisco
dc.description.fil
Fil: Martini, María Carla. Worcester Polytechnic Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Hicks, Nathan D.. Harvard University. Harvard School of Public Health; Estados Unidos
dc.description.fil
Fil: Xiao, Junpei. Worcester Polytechnic Institute; Estados Unidos
dc.description.fil
Fil: Alonso, Maria Natalia. Worcester Polytechnic Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Barbier, Thibault. Harvard University. Harvard School of Public Health; Estados Unidos
dc.description.fil
Fil: Sixsmith, Jaimie. Harvard University. Harvard School of Public Health; Estados Unidos
dc.description.fil
Fil: Fortune, Sarah M.. Harvard University. Harvard School of Public Health; Estados Unidos
dc.description.fil
Fil: Shell, Scarlet S.. Worcester Polytechnic Institute; Estados Unidos
dc.journal.title
Plos Pathogens
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.ppat.1010705
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010705
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