title: Downregulation of the Host Gene jigr1 by miR-92 Is Essential for Neuroblast Self-Renewal in Drosophila.
abstract: Intragenic microRNAs (miRNAs), located mostly in the introns of protein-coding genes, are often co-expressed with their host mRNAs. However, their functional interaction in development is largely unknown. Here we show that in Drosophila, miR-92a and miR-92b are embedded in the intron and 3'UTR of jigr1, respectively, and co-expressed with some jigr1 isoforms. miR-92a and miR-92b are highly expressed in neuroblasts of larval brain where Jigr1 expression is low. Genetic deletion of both miR-92a and miR-92b demonstrates an essential cell-autonomous role for these miRNAs in maintaining neuroblast self-renewal through inhibiting premature differentiation. We also show that miR-92a and miR-92b directly target jigr1 in vivo and that some phenotypes due to the absence of these miRNAs are partially rescued by reducing the level of jigr1. These results reveal a novel function of the miR-92 family in Drosophila neuroblasts and provide another example that local negative feedback regulation of host genes by intragenic miRNAs is essential for animal development.
authors.affiliation: Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: Yeliz
authors.initials: Y
authors.lastname: Yuva-Aydemir
authors.affiliation: Gladstone Institute of Neurological Disease, San Francisco, California, United States of America.
authors.forename: Xia-Lian
authors.initials: XL
authors.lastname: Xu
authors.affiliation: Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: Ozkan
authors.initials: O
authors.lastname: Aydemir
authors.affiliation: Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Gascon
authors.affiliation: Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: Serkan
authors.initials: S
authors.lastname: Sayin
authors.affiliation: Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Wenke
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Yang
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: Fen-Biao
authors.initials: FB
authors.lastname: Gao
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007814:Larva / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C000606970:Jigr1 protein, Drosophila; C576274:MIRN92 microRNA, Drosophila; D035683:MicroRNAs; D012333:RNA, Messenger