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SRX9743940: GSM4991182: 13-1-W Wild type, 360 min after mock treatment; Methylorubrum extorquens; RNA-Seq
4 ILLUMINA (NextSeq 500) runs: 16.3M spots, 1.2G bases, 479.8Mb downloads

Submitted by: NCBI (GEO)
Study: Global transcriptional response of Methylorubrum extorquens to formaldehyde stress includes both overlapping and unique gene sets in comparison to antibiotic translational inhibition and expands the role of EfgA
show Abstracthide Abstract
The potency and indiscriminate nature of formaldehyde reactivity upon biological molecules make it a universal stressor. However, some organisms such as Methylorubrum extorquens possess means to rapidly and effectively mitigate formaldehyde-induced damage. EfgA is a recently identified formaldehyde sensor predicted to halt translation in response to elevated formaldehyde as a means to protect cells. Herein, we investigate growth, formaldehyde consumption, and changes in gene expression to better understand how M. extorquens responds to formaldehyde with and without the EfgA-formaldehyde-mediated translational response, and how this mechanism compares to other forms of translation inhibition. These distinct mechanisms of translation inhibition have notable differences: they each involve different specific players and in addition, formaldehyde also acts as a general, multi-target stressor and a potential carbon source. Here, we present findings demonstrating that in addition to its characterized impact on translation, functional EfgA also allows for a rapid and robust transcriptional response to formaldehyde and that removal of efgA leads to heightened proteotoxic and genotoxic stress in the presence of increased formaldehyde levels. As our previous work suggested that formaldehyde is proteotoxic in M. extorquens, we accurately predicted that strains lacking efgA would experience increased protein damage. We also found that many downstream consequences of translation inhibition were shared by EfgA-formaldehyde- and kanamycin-mediated translation inhibition. Our work to modularize the transcriptional response uncovered additional layers of regulatory control enacted by functional EfgA upon experiencing formaldehyde stress, and further demonstrate the importance this protein plays at both transcriptional and translational levels in this model methylotroph. Overall design: Time courses of gene expression after treatment with two different translational inhibitors (kanamycin and formaldehyde). The responses of wild type and an ?efgA mutant of Methylorubrum extorquens were compared.
Sample: 13-1-W Wild type, 360 min after mock treatment
SAMN17172655 • SRS7931815 • All experiments • All runs
Library:
Instrument: NextSeq 500
Strategy: RNA-Seq
Source: TRANSCRIPTOMIC
Selection: cDNA
Layout: SINGLE
Construction protocol: RNA was purified from cells for each sample using the RNAsnap method [1]. First, cell pellets were resuspended in 500 µl of RNA extraction buffer (18 mM EDTA, 0.025% w/v SDS, 1% v/v 2-mercaptoethanol, 95% v/v formamide) by vortexing. Following incubation at 95°C for 7 min, cell debris was pelleted by centrifugation at 16000 × g for 5 min at room temperature. The resulting supernatant was purified using the Clean & Concentrator kit incorporating the on-column DNase digestion step (Zymo Research). Yields were determined using a Qubit 2.0 fluorometer with the RNA BR assay kit (ThermoFisher). Then, 1.5 µg of purified RNA for each sample was processed using the Ribozero rRNA Removal Kit (Gram-negative bacteria) (Illumina) according to the manufacturer's instructions except that reaction volumes were reduced by 50%. Depleted RNA samples were ethanol precipitated. RNA-Seq library preparation from rRNA-depleted samples began by fragmenting them with the NEBNext Magnesium RNA Fragmentation Module (New England Biolabs) for 110 s followed by ethanol precipitation. Fragmented RNA was treated with 10 U of T4 polynucleotide kinase (NEB) in 20 µl reactions containing 1 mM ATP. After another ethanol precipitation, the NEBNext small RNA Library Prep Set for Illumina (Multiplex Compatible) (New England Biolabs) was used to prepare samples according to recommended protocol, except all reaction volumes were reduced 50% and the SR RT primer concentration was reduced by an additional 50% in the RT primer hybridization step. After performing 15 cycles of PCR, samples were ethanol precipitated, and the DNA concentration was determined via the Qubit HS dsDNA assay kit (Thermofisher). For each sample, 200 ng of DNA was run on a 4% EX E-gel (ThermoFisher). DNA with a size of at least ~200 bases was excised and purified using a gel DNA recovery kit (Zymo Research) with elution in 50 µl of nuclease-free water.
Experiment attributes:
GEO Accession: GSM4991182
Links:
Runs: 4 runs, 16.3M spots, 1.2G bases, 479.8Mb
Run# of Spots# of BasesSizePublished
SRR133162874,130,860309.8M121.2Mb2021-01-01
SRR133162884,051,726303.9M118.5Mb2021-01-01
SRR133162894,100,594307.5M121.2Mb2021-01-01
SRR133162904,025,429301.9M118.9Mb2021-01-01

ID:
12743393

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