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SRX4993248: GSM3463228: DMS-MaPseq on in vitro refolded E. coli total RNA; Escherichia coli; OTHER
1 ILLUMINA (NextSeq 500) run: 35.2M spots, 2.7G bases, 931.2Mb downloads

Submitted by: NCBI (GEO)
Study: In vivo analysis of Influenza A mRNA secondary structures identifies critical regulatory motifs
show Abstracthide Abstract
The Influenza A virus (IAV) is a continuous health threat to humans as well as animals due to its high mutational rate and recurring epidemics and pandemics. The IAV genome is segmented and the eight negative-sense viral RNAs (vRNAs) are transcribed into positive sense RNAs (cRNAs) and viral messenger RNAs (vmRNAs) inside infected host cells. A role for the secondary structure of vmRNAs has been hypothesized and debated for many years, but knowledge on the structure vmRNAs adopt in vivo is currently missing. Here we solve, for the first time, the in vivo secondary structure of vmRNAs in living infected cells. We demonstrate that, compared to the in vitro refolded structure, in vivo vmRNAs are more unstructured but exhibit specific locally stable elements. Moreover, we show that the targeted disruption of these high-confidence structured domains results in an extraordinary attenuation of IAV replicative capacity. Collectively, our data provide the first comprehensive map of the in vivo structural landscape of IAV vmRNAs, hence providing the means for the development of new RNA-targeted antivirals. Overall design: RNA structure probing
Sample: DMS-MaPseq on in vitro refolded E. coli total RNA
SAMN10392653 • SRS4028716 • All experiments • All runs
Library:
Instrument: NextSeq 500
Strategy: OTHER
Source: TRANSCRIPTOMIC
Selection: other
Layout: SINGLE
Construction protocol: Cell pellets from exponential phase E. coli were resuspended in 1 ml of Resuspension Buffer [15 mM Tris-HCl pH 8.0; 450 mM Sucrose; 8 mM EDTA], and 18,500 U of Ready-Lyse Lysozyme (Epicentre, #R1810M) were added. After incubation at 22 °C for 5 min and on ice for 10 min, protoplasts were collected by centrifugation at 5000 x g (4 °C) for 5 min. Pellets were resuspended in 120 µl Protoplast Lysis Buffer [50 mM HEPES pH 8.0; 200 mM NaCl; 5 mM MgCl2; 1.5% SDS]. Samples were incubated for 5 min at 22 °C and for 5 min on ice, followed by addition of 30µl SDS precipitation buffer (50mM HEPES pH8, 1M KOAc, 5mM MgCl2). The precipitate was removed by centrifugation at 17000g (4 °C) for 5min and the supernatant was then extracted with TRIzol reagent, as per manufacturer instructions. RNA was fragmented in 64 mM Tris-HCl pH 8.3, 96 mM KCl, 3.9 mM MgCl2 for 8 min at 94 °C and subsequently purified on RNA Clean & Concentrator-5 columns. Reverse transcription (RT) was performed using the TGIRT-III enzyme (InGex, #TGIRT50) as described previously (Zubradt et al., 2016). Briefly, to the 5 µl of fragmented RNA, 1 µl 10 mM dNTPs and 0.5 µl 10 µM random hexamers were added, and the mixture was heated to 70 °C for 5 min and immediately placed on ice for 1 min. 2 µl of 5X RT Buffer [250 mM Tris-HCl pH 8.3; 375 mM KCl; 15 mM MgCl2], DTT to 5 mM, 10 U SUPERase In RNase Inhibitor, and 100 U TGIRT-III were added. Reverse transcription was then allowed to proceed at 25 °C for 5 min, followed by 1.5 h at 57 °C. To remove TGIRT-III from the RNA-DNA duplex, 1 µl of proteinase K was added to a final concentration of 0.1 µg/µl and the reaction incubated at 37 °C for 15 min., 1 µl of a 1:2 dilution of protease inhibitor cocktail (Sigma Aldrich, #P8340) was then added to inhibit proteinase K activity. The reaction volume was then adjusted to 25 µl by adding 3 µl of 5X RT Buffer and 10 µl water. Libraries were then prepared using the TruSeq RNA Library Prep Kit v2 (Illumina, #15025063), starting from second strand synthesis.
Experiment attributes:
GEO Accession: GSM3463228
Links:
Runs: 1 run, 35.2M spots, 2.7G bases, 931.2Mb
Run# of Spots# of BasesSizePublished
SRR817270535,238,2572.7G931.2Mb2019-05-07

ID:
6726967

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