title: Genome-wide impact of a recently expanded microRNA cluster in mouse.
abstract: Variations in microRNA (miRNA) gene and/or target repertoire are likely to be key drivers of phenotypic differences between species. To better understand these changes, we developed a computational method that identifies signatures of species-specific target site gain and loss associated with miRNA acquisition. Interestingly, several of the miRNAs implicated in mouse 3' UTR evolution derive from a single rapidly expanded rodent-specific miRNA cluster. Located in the intron of Sfmbt2, a maternally imprinted polycomb gene, these miRNAs (referred to as the Sfmbt2 cluster) are expressed in both embryonic stem cells and the placenta. One abundant miRNA from the cluster, miR-467a, functionally overlaps with the mir-290-295 cluster in promoting growth and survival of mouse embryonic stem cells. Predicted novel targets of the remaining cluster members are enriched in pathways regulating cell survival. Two relevant species-specific target candidates, Lats2 and Dedd2, were validated in cultured cells. We suggest that the rapid evolution of the Sfmbt2 cluster may be a result of intersex conflict for growth regulation in early mammalian development and could provide a general model for the genomic response to acquisition of miRNAs and similar regulatory factors.
authors.affiliation: MIT Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA.
authors.forename: Grace X Y
authors.initials: GX
authors.lastname: Zheng
authors.forename: Arvind
authors.initials: A
authors.lastname: Ravi
authors.forename: Genevieve M
authors.initials: GM
authors.lastname: Gould
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Burge
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Sharp
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D002874:Chromosome Mapping; D053487:DEAD-box RNA Helicases / Q000235:genetics; D053595:Embryonic Stem Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D016678:Genome / Q000235:genetics*; D006801:Humans; D051379:Mice / Q000235:genetics*; D018345:Mice, Knockout; D035683:MicroRNAs / Q000145:classification / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D034622:RNA Interference; D012097:Repressor Proteins; D043244:Ribonuclease III / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D012097:Repressor Proteins; C527638:Sfmbt2 protein, mouse; D014157:Transcription Factors; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases