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Relaxed selection drives a noisy noncoding transcriptome in members of the Mycobacterium tuberculosis complex.

Dinan AM, Tong P, Lohan AJ, Conlon KM, Miranda-CasoLuengo AA, Malone KM, Gordon SV, Loftus BJ - MBio (2014)

Bottom Line: A small number of studies have compared the primary transcriptomes of different bacterial species, but few have compared closely related species with clearly divergent evolutionary histories.We show that a species population history is reflected in its transcriptome and posit relaxed selection as the main driver of an abundance of canonical -10 promoter sites in M. bovis relative to M. marinum.Finally, through comparison of M. bovis and M. tuberculosis, we illustrate that single nucleotide polymorphism (SNP)-driven promoter differences likely underpin many of the transcriptional differences between M. tuberculosis complex lineages.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Cell Biology Centre, The University of Edinburgh, Edinburgh, United Kingdom.

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Conservation of attenuation patterns in the 5′ UTRs of whiB7. Transcription initiates at conserved primary TSSs located ~350 nt upstream of the whiB7 start codons and peaks in both species within the indicated upstream ORFs (uORFs). Transcriptional attenuation then occurs at the 3′ ends of the uORFs, proximal to a conserved stem-loop structure followed by a U-rich stretch, predicted to function as a rho-independent terminator (RIT).
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fig4: Conservation of attenuation patterns in the 5′ UTRs of whiB7. Transcription initiates at conserved primary TSSs located ~350 nt upstream of the whiB7 start codons and peaks in both species within the indicated upstream ORFs (uORFs). Transcriptional attenuation then occurs at the 3′ ends of the uORFs, proximal to a conserved stem-loop structure followed by a U-rich stretch, predicted to function as a rho-independent terminator (RIT).

Mentions: For example, the gene whiB7, which is upregulated in response to a variety of antibiotics and regulates the expression of a number of proteins involved in intrinsic antibiotic resistance (24), was found to have prominent 5′ UTR expression relative to that of its CDS in both species (Fig. 4). Within the 5′ UTRs of whiB7 in both species, we identified a small, unannotated upstream open reading frame (uORF) located ~10 nt downstream of a consensus Shine-Dalgarno (SD) motif. Transcription is seen to spike at the 5′ of the uORF and attenuates rapidly 3′ of the uORF, consistent with the presence of a conserved stem-loop structure with a T-rich tail, which may function as a rho-independent terminator (RIT) (Fig. 4). Previous studies have identified this ORF upstream of whiB7 in M. tuberculosis and have shown that whiB7 is transcriptionally coupled to it (25). Our data showing that the uORF and whiB7 have been cotranscribed across evolutionary time provide a strong case for its involvement in the regulation of whiB7 expression.


Relaxed selection drives a noisy noncoding transcriptome in members of the Mycobacterium tuberculosis complex.

Dinan AM, Tong P, Lohan AJ, Conlon KM, Miranda-CasoLuengo AA, Malone KM, Gordon SV, Loftus BJ - MBio (2014)

Conservation of attenuation patterns in the 5′ UTRs of whiB7. Transcription initiates at conserved primary TSSs located ~350 nt upstream of the whiB7 start codons and peaks in both species within the indicated upstream ORFs (uORFs). Transcriptional attenuation then occurs at the 3′ ends of the uORFs, proximal to a conserved stem-loop structure followed by a U-rich stretch, predicted to function as a rho-independent terminator (RIT).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128351&req=5

fig4: Conservation of attenuation patterns in the 5′ UTRs of whiB7. Transcription initiates at conserved primary TSSs located ~350 nt upstream of the whiB7 start codons and peaks in both species within the indicated upstream ORFs (uORFs). Transcriptional attenuation then occurs at the 3′ ends of the uORFs, proximal to a conserved stem-loop structure followed by a U-rich stretch, predicted to function as a rho-independent terminator (RIT).
Mentions: For example, the gene whiB7, which is upregulated in response to a variety of antibiotics and regulates the expression of a number of proteins involved in intrinsic antibiotic resistance (24), was found to have prominent 5′ UTR expression relative to that of its CDS in both species (Fig. 4). Within the 5′ UTRs of whiB7 in both species, we identified a small, unannotated upstream open reading frame (uORF) located ~10 nt downstream of a consensus Shine-Dalgarno (SD) motif. Transcription is seen to spike at the 5′ of the uORF and attenuates rapidly 3′ of the uORF, consistent with the presence of a conserved stem-loop structure with a T-rich tail, which may function as a rho-independent terminator (RIT) (Fig. 4). Previous studies have identified this ORF upstream of whiB7 in M. tuberculosis and have shown that whiB7 is transcriptionally coupled to it (25). Our data showing that the uORF and whiB7 have been cotranscribed across evolutionary time provide a strong case for its involvement in the regulation of whiB7 expression.

Bottom Line: A small number of studies have compared the primary transcriptomes of different bacterial species, but few have compared closely related species with clearly divergent evolutionary histories.We show that a species population history is reflected in its transcriptome and posit relaxed selection as the main driver of an abundance of canonical -10 promoter sites in M. bovis relative to M. marinum.Finally, through comparison of M. bovis and M. tuberculosis, we illustrate that single nucleotide polymorphism (SNP)-driven promoter differences likely underpin many of the transcriptional differences between M. tuberculosis complex lineages.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Cell Biology Centre, The University of Edinburgh, Edinburgh, United Kingdom.

Show MeSH
Related in: MedlinePlus