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Series GSE34475 Query DataSets for GSE34475
Status Public on Mar 01, 2012
Title Degradation of cellular miR-27 by a novel, highly abundant viral transcript is important for efficient virus replication in vivo.
Organism Mus musculus
Experiment type Non-coding RNA profiling by high throughput sequencing
Summary Cytomegaloviruses express large amounts of viral miRNAs during lytic infection, yet, they only modestly alter the cellular miRNA profile. The most prominent alteration upon lytic murine cytomegalovirus (MCMV) infection is the rapid degradation of the cellular miR-27a and miR-27b. Here, we report that this regulation is mediated by the <1.7 kb spliced and highly abundant MCMV m169 transcript. Specificity to miR-27a/b is mediated by a single, apparently optimized, miRNA binding site located in its 3'-UTR. This site is easily and efficiently retargeted to other cellular and viral miRNAs by target site replacement. Expression of the 3'-UTR of m169 by an adenoviral vector was sufficient to mediate its function, indicating that no other viral factors are essential in this process. Degradation of miR-27a/b was found to be accompanied by 3'-tailing and -trimming. Despite its dramatic effect on miRNA stability, we found this interaction to be mutual, indicating potential regulation of m169 by miR-27a/b. Most interestingly, three mutant viruses no longer able to target miR-27a/b, either due to miRNA target site disruption or target site replacement, showed significant attenuation in multiple organs as early as 4 days post infection, indicating that degradation of miR-27a/b is important for efficient MCMV replication in vivo.
Overall design Small RNA sequencing from total RNA or Ago2 associated small RNAs extracted from mock- or MCMV-infected NIH-3T3 cells
Contributor(s) Marcinowski L, Tanguy M, Krmpotic A, Rädle B, Lisnić VJ, Tuddenham L, Chane-Woon-Ming B, Ruzsics Z, Erhard F, Benkartek C, Babic M, Zimmer R, Trgovcich J, Koszinowski U, Jonjic S, Pfeffer S, Dölken L
Citation(s) 22346748
Submission date Dec 15, 2011
Last update date May 15, 2019
Contact name Sébastien Pfeffer
Organization name CNRS - Institut de Biologie Moléculaire et Cellulaire (IBMC)
Department UPR 9002 - Architecture et Réactivité de l'ARN
Lab RNA regulation in viral infections
Street address 2 allée Konrad Roentgen
City Strasbourg
ZIP/Postal code 67084
Country France
Platforms (1)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (4)
GSM849855 Total RNA extracted from mock infected NIH-3T3 cells
GSM849856 Total RNA extracted from MCMV infected NIH-3T3 cells
GSM849857 Ago 2 immunoprecipitated RNA extracted from mock infected NIH-3T3 cells
SRA SRP009848
BioProject PRJNA151355

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