The Mycobacterium tuberculosis sRNA F6 Modifies Expression of Essential Chaperonins, GroEL2 and GroES

Abstract

Control of gene expression via small regulatory RNAs (sRNAs) is poorly understood in one of the most successful pathogens, Mycobacterium tuberculosis . Here, we present an in-depth characterization of the sRNA F6, including its expression in different infection models and the differential gene expression observed upon deletion of the sRNA.

Using a whole genome co‐expression network to inform the functional characterisation of predicted genomic elements from Mycobacterium tuberculosis transcriptomic data

“…Mcr7/ncRv2395A, found to be part of the PhoP regulon (Solans et al, 2014), is a hub in the ‘violet’ module enriched for lipid metabolism and PE/PPE functional categories, correlated positively with growth in cholesterol (bicor = 0.35, p adj = 0.04) and butyrate (bicor = 0.41, p adj = 0.02) and negatively correlated with low iron (bicor = −0.36, p adj = 0.03) (Figure 3). F6/ncRv10243/SfdS, a sRNA upregulated in starvation and mouse infection models, is thought to be involved in regulating lipid metabolism and long‐term persistence (Houghton et al, 2021). This ncRNA is a hub in a module found to be enriched in ‘lipid metabolism’ genes ( ‘saddlebrown’ ) and found to be correlated positively with reaerated culture (bicor = 0.38, p adj = 0.04) and butyrate (bicor = 0.4, p adj = 0.02) conditions (Figure 3).…”

“…(bicor = −0.36, p adj = 0.03) (Figure 3). F6/ncRv10243/SfdS, a sRNA upregulated in starvation and mouse infection models, is thought to be involved in regulating lipid metabolism and long-term persistence (Houghton et al, 2021). This ncRNA is a hub in a module found to be enriched in 'lipid metabolism' genes ('saddlebrown') and found to be correlated positively with reaerated culture (bicor = 0.38, p adj = 0.04) and butyrate (bicor = 0.4, p adj = 0.02) conditions (Figure 3).…”

Using a Whole Genome Co-expression Network to Inform the Functional Characterisation of Predicted Genomic Elements fromMycobacterium tuberculosisTranscriptomic Data

“…Mcr7/ncRv2395A, found to be part of the PhoP regulon (Solans et al, 2014), is a hub in the ‘magenta’ module enriched for elements in the KEGG pathway for valine, leucine and isoleucine degradation and correlated positively with the low iron condition (Figure 3). F6/ncRv10243/SfdS, a sRNA upregulated in starvation and mouse infection models, is thought to be involved in regulating lipid metabolism and long-term persistence (Houghton et al, 2021). This ncRNA is a hub in a module found to be enriched for the GO terms ‘lipid metabolism’ and ‘biosynthesis of fatty acids’ ( ‘lightcyan’ ) and found to be correlated positively with low iron and negatively with extended hypoxia conditions (Figure 3).…”

“…The hubs of the ‘lightcyan’ module include several predicted sRNAs, and the annotated sRNA, F6. F6/ncRv10243/SfdS is a sigF-dependent ncRNA which has been shown to be induced in nutrient starvation, oxidative stress, acid stress (Arnvig & Young, 2009; Houghton et al, 2021) and the fatty acid hypoxia model (Del Portillo et al, 2019). In addition to being expressed from its own promoter, F6/SfdS has been proposed to be co-transcribed with the upstream gene fadA2 (Rv0243), a probable acetyl-CoA acyltransferase; however, fadA2 is clustered in a different module from SfdS, one associated with iron acquisition (‘ violet’, see below).…”

“…Mcr7/ncRv2395A, found to be part of the PhoP regulon (Solans et al, 2014), is a hub in the ‘violet’ module enriched for lipid metabolism and PE/PPE functional categories, correlated positively with growth in cholesterol (bicor= 0.35, p adj = 0.04) and butyrate (bicor= 0.41, p adj = 0.02) and negatively correlated with low iron (bicor= −0.36, p adj = 0.03) (Figure 3). F6/ncRv10243/SfdS, a sRNA upregulated in starvation and mouse infection models, is thought to be involved in regulating lipid metabolism and long-term persistence (Houghton et al, 2021). This ncRNA is a hub in a module found to be enriched in ‘lipid metabolism’ genes ( ‘saddlebrown’ ) and found to be correlated positively with reaerated culture (bicor= 0.38, p adj = 0.04) and butyrate (bicor= 0.4, p adj = 0.02) conditions (Figure 3).…”