title: Characterizing isomiR variants within the microRNA-34/449 family.
abstract: miR-34/449 microRNAs are conserved regulators of multiciliated cell differentiation. Here, we evidence and characterize expression of two isomiR variant sequences from the miR-34/449 family in human airway epithelial cells. These isomiRs differ from their canonical counterparts miR-34b and miR-449c by one supplemental uridine at their 5'-end, leading to a one-base shift in their seed region. Overexpression of canonical miR-34/449 or 5'-isomiR-34/449 induces distinct gene expression profiles and biological effects. However, some target transcripts and functional activities are shared by both canonical microRNAs and isomiRs. Indeed, both repress important targets that result in cell cycle blockage and Notch pathway inhibition. Our findings suggest that 5'-isomiR-34/449 may represent additional mechanisms by which miR-34/449 family finely controls several pathways to drive multiciliogenesis.
authors.affiliation: CNRS, IPMC, Université Côte d'Azur, Sophia-Antipolis, Valbonne, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Mercey
authors.affiliation: CNRS, IPMC, Université Côte d'Azur, Sophia-Antipolis, Valbonne, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Popa
authors.affiliation: CNRS, IPMC, Université Côte d'Azur, Sophia-Antipolis, Valbonne, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Cavard
authors.affiliation: CNRS, IPMC, Université Côte d'Azur, Sophia-Antipolis, Valbonne, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Paquet
authors.affiliation: CNRS, IPMC, Université Côte d'Azur, Sophia-Antipolis, Valbonne, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Chevalier
authors.affiliation: CNRS, IPMC, Université Côte d'Azur, Sophia-Antipolis, Valbonne, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pons
authors.affiliation: CNRS, IPMC, Université Côte d'Azur, Sophia-Antipolis, Valbonne, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Magnone
authors.affiliation: CNRS, INSERM, IRCAN, FHU-OncoAge, Université Côte d'Azur, Sophia-Antipolis, Valbonne, France.
authors.forename: Joséphine
authors.initials: J
authors.lastname: Zangari
authors.affiliation: CNRS, INSERM, IRCAN, FHU-OncoAge, Université Côte d'Azur, Sophia-Antipolis, Valbonne, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Brest
authors.affiliation: CNRS, IPMC, Université Côte d'Azur, Sophia-Antipolis, Valbonne, France.
authors.forename: Laure-Emmanuelle
authors.initials: LE
authors.lastname: Zaragosi
authors.affiliation: CNRS, IPMC, Université Côte d'Azur, Sophia-Antipolis, Valbonne, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Ponzio
authors.affiliation: CNRS, IPMC, Université Côte d'Azur, Sophia-Antipolis, Valbonne, France.
authors.forename: Kevin
authors.initials: K
authors.lastname: Lebrigand
authors.affiliation: CNRS, IPMC, Université Côte d'Azur, Sophia-Antipolis, Valbonne, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Barbry
authors.affiliation: CNRS, IPMC, Université Côte d'Azur, Sophia-Antipolis, Valbonne, France.
authors.forename: Brice
authors.initials: B
authors.lastname: Marcet
mesh_terms: D000072283:A549 Cells; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009297:Nasal Mucosa / Q000166:cytology / Q000378:metabolism; D061251:Primary Cell Culture; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta / Q000235:genetics / Q000378:metabolism
chemical_list: C569658:ARHGDIB protein, human; C522425:MIRN34 microRNA, human; C544530:MIRN449 microRNA, human; D035683:MicroRNAs; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; C085929:RRAS protein, human; D018631:ras Proteins
keywords: isomiR; miR-34; miR-449; miRBase; microRNA; multiciliated cell