Cis regulation within a cluster of viral microRNAs

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Vilimova , M , Contrant , M , Randrianjafy , R , Dumas , P , Elbasani , E , Ojala , P M , Pfeffer , S & Fender , A 2021 , ' Cis regulation within a cluster of viral microRNAs ' , Nucleic Acids Research , vol. 49 , no. 17 , pp. 10018-10033 .

Title: Cis regulation within a cluster of viral microRNAs
Author: Vilimova, Monika; Contrant, Maud; Randrianjafy, Ramy; Dumas, Philippe; Elbasani, Endrit; Ojala, Päivi M.; Pfeffer, Sebastien; Fender, Aurelie
Contributor organization: CAN-PRO - Translational Cancer Medicine Program
Department of Pathology
Date: 2021-09-27
Language: eng
Number of pages: 16
Belongs to series: Nucleic Acids Research
ISSN: 0305-1048
Abstract: MicroRNAs (miRNAs) are small regulatory RNAs involved in virtually all biological processes. Although many of them are co-expressed from clusters, little is known regarding the impact of this organization on the regulation of their accumulation. In this study, we set to decipher a regulatory mechanism controlling the expression of the ten clustered pre-miRNAs from Kaposi's sarcoma associated herpesvirus (KSHV). We measured in vitro the efficiency of cleavage of each individual pre-miRNA by the Microprocessor and found that pre-miR-K1 and -K3 were the most efficiently cleaved pre-miRNAs. A mutational analysis showed that, in addition to producing mature miRNAs, they are also important for the optimal expression of the whole set of miRNAs. We showed that this feature depends on the presence of a canonical pre-miRNA at this location since we could functionally replace pre-miR-K1 by a heterologous pre-miRNA. Further in vitro processing analysis suggests that the two stem-loops act in cis and that the cluster is cleaved in a sequential manner. Finally, we exploited this characteristic of the cluster to inhibit the expression of the whole set of miRNAs by targeting the premiR-K1 with LNA-based antisense oligonucleotides in cells either expressing a synthetic construct or latently infected with KSHV.
Description: Correction: Volume49, Issue18 Page10804-10805 Article Number711910 DOI10.1093/nar/gkab806
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by_nc
Usage restriction: openAccess
Self-archived version: publishedVersion

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