title: Novel regulation and functional interaction of polycistronic miRNAs.
abstract: The importance of microRNAs in gene expression and disease is well recognized. However, what is less appreciated is that almost half of miRNA genes are organized in polycistronic clusters and are therefore coexpressed. The mir-11∼998 cluster consists of two miRNAs, miR-11 and miR-998. Here, we describe a novel layer of regulation that links the processing and expression of miR-998 to the presence of the mir-11 gene. We show that the presence of miR-11 in the pri-miRNA is required for processing by Drosha, and deletion of mir-11 prevents the expression of miR-998. Replacing mir-11 with an unrelated miRNA rescued miR-998 expression in vivo and in vitro, as did expressing miR-998 from a shorter, more canonical miRNA scaffold. The embedded regulation of miR-998 is functionally important because unchecked miR-998 expression in the absence of miR-11 resulted in pleiotropic developmental defects. This novel regulation of expression of miRNAs within a cluster is not limited to the mir-11∼998 cluster and, thus, likely reflects the more general cis-regulation of expression of individual miRNAs. Collectively, our results uncover a novel layer of regulation within miRNA clusters that tempers the functions of the individual miRNAs. Unlinking their expression has the potential to change the expression of multiple miRNA targets and shift a biological response.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Truscott
authors.affiliation: Department of Genetic Engineering and Biotechnology, University of Dhaka, Dhaka 1000, Bangladesh.
authors.forename: Abul B M M K
authors.initials: AB
authors.lastname: Islam
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
authors.forename: Maxim V
authors.initials: MV
authors.lastname: Frolov
mesh_terms: D000483:Alleles; D000818:Animals; D002478:Cells, Cultured; D004330:Drosophila; D005786:Gene Expression Regulation; D035683:MicroRNAs / Q000235:genetics*
chemical_list: D035683:MicroRNAs
keywords: cis-regulation of miRNA expression; miRNA biogenesis; miRNA cluster; polycistronic miRNA