title: MicroRNAs act as cofactors in bicoid-mediated translational repression.
abstract: Noncoding RNAs have recently emerged as important regulators of mRNA translation and turnover [1, 2]. Nevertheless, we largely ignore how their function integrates with protein-mediated translational regulation. We focus on Bicoid, a key patterning molecule in Drosophila, which inhibits the translation of caudal in the anterior part of the embryo [3, 4]. Previous work showed that Bicoid recruits the cap-binding protein d4EHP on the caudal mRNA to repress translation [5]. Here we show that miR-2 family microRNAs are essential cofactors in the repression of caudal. Using an in vivo sensor, we demonstrate that Bicoid acts through a 63 nt response element in the caudal 3' UTR that includes a single miR-2 target site. Mutating that site abolishes Bicoid-mediated repression, and this effect can be partly reversed by expressing a microRNA with compensatory changes that restore binding to the mutated target. Four predicted Bicoid splice isoforms are capable of caudal repression, including two that lack the d4EHP interaction domain; all four isoforms require the microRNA target for repression. The synergy between Bicoid and microRNAs appears to have evolved recently in the context of the drosophilid caudal BRE. The discovery that microRNAs play an essential role in Bicoid-mediated translational repression opens up new perspectives on Bicoid's function and evolution.
authors.affiliation: Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research and Technology Hellas (FoRTH), 70013 Heraklio, Crete, Greece.
authors.forename: Claudia J
authors.initials: CJ
authors.lastname: Rödel
authors.forename: Anna F
authors.initials: AF
authors.lastname: Gilles
authors.forename: Michalis
authors.initials: M
authors.lastname: Averof
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; C056478:bcd protein, Drosophila; C084564:cad protein, Drosophila