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SRX19124256: GSM6947268: Fs+Ar total RNA EMBR; Fibrobacter succinogenes; Anaeromyces robustus; OTHER
1 ILLUMINA (Illumina HiSeq 4000) run: 13.4M spots, 4G bases, 1.9Gb downloads

External Id: GSM6947268_r1
Submitted by: Chemical Engineering, University of California Santa Barbara
Study: Bacterial mRNA sequencing through targeted rRNA depletion for efficient RNA-seq in varied species and co-cultures
show Abstracthide Abstract
mRNA sequencing in bacteria is challenging due to the abundance of ribosomal rRNA that cannot be easily removed prior to sequencing. While commercially available kits target specific rRNA sequences found in defined lists of common bacterial species, they are frequently inefficient when applied to other divergent species, including those from environmental isolates. Similar to the commercial kits, other common techniques for rRNA depletion typically employ large probe sets that tile full-length rRNA sequences; however, such approaches are both time consuming and expensive when applied to multiple species or complex consortia of non-model microbes. To overcome these limitations, we present EMBR-seq+, which employs less than twenty target oligonucleotides per rRNA molecule, and builds upon our previous rRNA depletion approach, EMBR-seq, through the addition of an RNase H depletion step, to achieve rRNA removal efficiencies of up to 99%. First, we applied EMBR-seq+ to monocultures of Escherichia coli, Geobacter metallireducens, and Fibrobacter succinogenes strain UWB7 to deplete rRNA to approximately 1-7% of the sequencing reads, demonstrating that the new method can be easily extended to diverse bacterial species. Further, in more complex co-cultures between F. succinogenes strain UWB7 and anerobic fungal species, we applied EMBR-seq+ to deplete both bacterial and fungal rRNA, with an approximately 4-fold improved bacterial rRNA depletion efficiency compared to a previous report using a commercial kit, thereby showing that the method can be effectively translated to non-model microbial mixtures. Notably, we also demonstrate that for microbial species with poorly annotated genomes and unknown rRNA sequences, the RNase H depletion component of EMBR-seq+ enables rapid iterations in probe design without requiring to start experiments from total RNA each time, and was key for depleting fungal rRNA to enrich the bacterial mRNA readout in co-cultures. Finally, efficient depletion of rRNA enabled systematic quantification of the reprogramming of the bacterial transcriptome when cultured in the presence of the anerobic fungi, Anaeromyces robustus and Caecomyces churrovis. We observed that F. succinogenes strain UWB7 transcribes nearly 200 carbohydrate-active enzyme (CAZyme) genes in both monoculture and co-culture conditions, with several lignocellulose-degrading CAZymes downregulated in the presence of an anerobic gut fungus. This finding is consistent with the premise that bacteria and fungi specialize in different aspects of biomass breakdown, such that the presence of one regulates the CAZyme production of the other. This also supports previous findings that the fungi release excess reducing sugars in the supernatant, which benefits other members of the microbial community. Thus EMBR-seq+ provides a new and detailed perspective of a rumen microbiome model system by dramatically improving the efficiency of mRNA sequencing, and more generally also enables high-throughput, cost-effective and rapid quantification of the transcriptome to gain functional insights into less-studied and non-model microbial systems. Overall design: We developed a method, EMBR-seq+, to efficiently sequence RNA from bacterial samples by depleting rRNA during the RNA library preparation. EMBR-seq+ combines our previous method, EMBR-seq, with RNase H treatment to achieve improved rRNA depletion. We demonstrated that rRNA is depleted to less than 10% of sequencing reads for monocultures of E. coli, G. metallireducens, and F. succinogenes strain UWB7 and less than 25% of bacterial reads for co-cultures of F. succinogenes strain UWB7 with either A. robustus or C. churrovis.
Sample: Fs+Ar total RNA EMBR
SAMN32819502 • SRS16523530 • All experiments • All runs
Library:
Name: GSM6947268
Instrument: Illumina HiSeq 4000
Strategy: OTHER
Source: TRANSCRIPTOMIC
Selection: other
Layout: PAIRED
Construction protocol: For E. coli and G. metallireducens monocultures, total RNA extractions were performed using Trizol according to the manufacturer's protocol. RNA was extracted from F. succinogenes strain UWB7 monoculture & co-culture pellets using the RNeasy Mini Kit following the protocol for purification of total RNA from plant cells and tissues and filamentous fungi, using liquid N2 method of cell lysis, QIAshredder homogenization, on-column DNase I digestion, and elution in 30 µL of RNAse-free water. (1) Overview: EMBR-seq libraries were prepared according to the protocol described in Wangsanuwat et al. 100 ng of total RNA were used as input material for all libraries. For the libraries denoted “EMBR-seq” and “EMBR-seq+”, blocking primers were added during the polyadenylation step and reverse transcription step. For the libraries denoted “No depletion” and “RNase H”, water was added instead of blocking primers during these two steps. In the libraries denoted “RNase H” and “EMBR-seq+”, the RNase H treatment was performed as described below. In the libraries denoted “No depletion” and “EMBR-seq”, the RNase H treatment was skipped; the amplified RNA (aRNA) product of in vitro transcription (IVT) was used directly for the library reverse transcription step as described in Wangsanuwat et al. (2) Polyadenylation: 2 μL of total RNA (50 ng/μL) was mixed with 1 μL of 5x first strand buffer [250 mM Tris-HCl (pH 8.3), 375 mM KCl, 15 mM MgCl2, comes with Superscript II reverse transcriptase, Invitrogen Cat. # 18064014], 1 uL of blocking primer mix, 0.1 μL 10 mM ATP, and 0.1 μL E. coli poly-A polymerase (New England Biolabs, Cat. # M0276S). The samples were incubated at 37°C for 10 mins. In the “No depletion” and “RNase H” libraries, 1 μL of nuclease-free water was added instead of the blocking primer mix. (3) Reverse transcription: The polyadenylation product was mixed with 0.5 μL 10 mM dNTPs (New England Biolabs, Cat. # N0447L), 1 μL reverse transcription primers (25 ng/μL, Supplementary Table 2), and 1.3 μL blocking primer mix, and heated to 65°C for 5 mins, 58°C for 1 min, and then quenched on ice. In the “No depletion” and “RNase H” libraries, 1.3 μL of nuclease-free water was added instead of the blocking primer mix. This product was then mixed with 1.2 μL 5x first strand buffer, 1 μL 0.1 M DTT, 0.5 μL RNaseOUT (Thermo Fisher Scientific, Cat. #10777019), and 0.5 μL Superscript II reverse transcriptase, and then incubated at 42°C for 1 hr. Immediately afterwards, the samples were heat-inactivated at 70°C for 10 mins. (4) Second strand synthesis: The reverse transcription product was mixed with 33.5 μL nuclease-free water, 12 μL 5x second strand buffer [100 mM Tris-HCl (pH 6.9), 23 mM MgCl2, 450 mM KCl, 0.75 mM β-NAD, 50 mM (NH4)2SO4, Invitrogen, Cat. # 10812014], 1.2 μL 10 mM dNTPs, 0.4 μL E. coli ligase (Invitrogen, Cat. # 18052019), 1.5 μL DNA polymerase I (Invitrogen, Cat. # 18010025), and 0.4 μL RNase H (Invitrogen, Cat. # 18021071), and incubated at 16°C for 2 hrs. The cDNA was purified with 1x AMPure XP DNA beads (Beckman Coulter, Cat. # A63881) and eluted in 24 μL nuclease-free water that was subsequently concentrated to 6.4 μL. (5) In vitro transcription: The product from the previous step was mixed with 9.6 μL of in vitro transcription mix (1.6 μL of each ribonucleotide, 1.6 μL 10x T7 reaction buffer, 1.6 μL T7 enzyme mix, MEGAscript T7 Transcription Kit, Thermo Fisher Scientific, Cat. # AMB13345) and incubated at 37°C for 13 hrs. The IVT product was mixed with 6 μL ExoSAP-IT PCR Product Cleanup Reagent (Thermo Fisher Scientific, Cat. # 78200.200.UL) and incubated at 37°C for 15 mins. Next, it was treated with 5.5 μL fragmentation buffer (200 mM Tris-acetate (pH 8.1), 500 mM KOAc, 150 mM MgOAc) at 94°C for 3 mins and immediately quenched with 2.75 μL stop buffer (0.5 M EDTA) on ice. The fragmented aRNA was size-selected with 0.8x AMPure RNA beads (RNAClean XP Kit, Beckman Coulter, Cat. # A63987) and eluted in 18 μL nuclease-free water. In the libraries denoted “No depletion” and “EMBR-seq”, the fragmented and cleaned-up in vitro transcription product was used directly for Illumina library preparation by reverse transcription and PCR, as described previously (18, 30). In the “
Runs: 1 run, 13.4M spots, 4G bases, 1.9Gb
Run# of Spots# of BasesSizePublished
SRR2317375113,357,0454G1.9Gb2023-09-30

ID:
26296734

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