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GEO help: Mouse over screen elements for information. |
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| Status |
Public on May 05, 2019 |
| Title |
In vivo analysis of Influenza A mRNA secondary structures identifies critical regulatory motifs |
| Organisms |
Escherichia coli; Influenza A virus |
| Experiment type |
Other
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| Summary |
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.
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| Overall design |
RNA structure probing
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| Contributor(s) |
Simon L, Morandi E, Luganini A, Gribaudo G, Martinez-Sobrido L, Turner DH, Oliviero S, Incarnato D |
| Citation(s) |
31053845 |
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| Submission date |
Nov 07, 2018 |
| Last update date |
May 17, 2019 |
| Contact name |
Danny Incarnato |
| E-mail(s) |
d.incarnato@rug.nl
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| Organization name |
University of Groningen
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| Department |
Molecular Genetics
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| Street address |
Nijenborgh 7
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| City |
Groningen |
| State/province |
Netherlands |
| ZIP/Postal code |
9747 AG |
| Country |
Netherlands |
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| Platforms (3) |
| GPL21222 |
Illumina NextSeq 500 (Escherichia coli) |
| GPL24947 |
Illumina MiSeq (Influenza A virus) |
| GPL25780 |
Illumina NextSeq 500 (Influenza A virus) |
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| Samples (20)
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| GSM3463226 |
DMS-MaPseq on denatured E. coli total RNA (Replicate #1) |
| GSM3463227 |
DMS-MaPseq on denatured E. coli total RNA (Replicate #2) |
| GSM3463228 |
DMS-MaPseq on in vitro refolded E. coli total RNA |
| GSM3463229 |
DMS-MaPseq on ex vivo native deproteinized E. coli total RNA (Replicate #1) |
| GSM3463230 |
DMS-MaPseq on ex vivo native deproteinized E. coli total RNA (Replicate #2) |
| GSM3463231 |
DMS-MaPseq on in vivo-purified denatured Influenza A vmRNA (Replicate #1) |
| GSM3463232 |
DMS-MaPseq on in vivo-purified denatured Influenza A vmRNA (Replicate #2) |
| GSM3463233 |
DMS-MaPseq on in vitro-transcribed denatured Influenza A vmRNA (Replicate #1) |
| GSM3463234 |
DMS-MaPseq on in vitro-transcribed denatured Influenza A vmRNA (Replicate #2) |
| GSM3463235 |
DMS-MaPseq on in vivo-purified Influenza A vmRNA (Replicate #1) |
| GSM3463236 |
DMS-MaPseq on in vivo-purified Influenza A vmRNA (Replicate #2) |
| GSM3463237 |
DMS-MaPseq on in vitro-transcribed and refolded Influenza A vmRNA (Replicate #1) |
| GSM3463238 |
DMS-MaPseq on in vitro-transcibed and refolded Influenza A vmRNA (Replicate #2) |
| GSM3463239 |
DMS-MaPseq on in vivo spliced segment 7/8 Influenza A vmRNAs (Replicate #1) |
| GSM3463240 |
DMS-MaPseq on in vivo spliced segment 7/8 Influenza A vmRNAs (Replicate #2) |
| GSM3463241 |
DMS-MaPseq on in vivo Influenza A vmRNA probe pairing regions (Replicate #1) |
| GSM3463242 |
DMS-MaPseq on in vivo Influenza A vmRNA probe pairing regions (Replicate #2) |
| GSM3463243 |
DMS-MaPseq on in vivo Influenza A vmRNA mutated structural motifs |
| GSM3463244 |
DMS-MaPseq on untreated in vivo-purified Influenza A vmRNA |
| GSM3463245 |
DMS-MaPseq on untreated in vitro-transcribed Influenza A vmRNA |
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| Relations |
| BioProject |
PRJNA504460 |
| SRA |
SRP168082 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE122286_RAW.tar |
760.0 Kb |
(http)(custom) |
TAR (of FASTA, WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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