title: A requirement for ERK-dependent Dicer phosphorylation in coordinating oocyte-to-embryo transition in C. elegans.
abstract: Signaling pathways and small RNAs direct diverse cellular events, but few examples are known of defined signaling pathways directly regulating small RNA biogenesis. We show that ERK phosphorylates Dicer on two conserved residues in its RNase IIIb and double-stranded RNA (dsRNA)-binding domains and that phosphorylation of these residues is necessary and sufficient to trigger Dicer's nuclear translocation in worms, mice, and human cells. Phosphorylation of Dicer on either site inhibits Dicer function in the female germline and dampens small RNA repertoire. Our data demonstrate that ERK phosphorylates and inhibits Dicer during meiosis I for oogenesis to proceed normally in Caenorhabditis elegans and that this inhibition is released before fertilization for embryogenesis to proceed normally. The conserved Dicer residues, their phosphorylation by ERK, and the consequences of the resulting modifications implicate an ERK-Dicer nexus as a fundamental component of the oocyte-to-embryo transition and an underlying mechanism coupling extracellular cues to small RNA production.
authors.affiliation: Department of Genetics, UT MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Drake
authors.affiliation: Department of Genetics, UT MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Tokiko
authors.initials: T
authors.lastname: Furuta
authors.affiliation: Department of Biochemistry and Molecular Biology, UT MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
authors.forename: Kin Man
authors.initials: KM
authors.lastname: Suen
authors.affiliation: Department of Genetics, UT MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Gonzalez
authors.affiliation: Center for Genetics and Genomics, UT MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Graduate Program in Diagnostic Genetics, School of Health Professions, UT MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Awdhesh
authors.initials: A
authors.lastname: Kalia
authors.affiliation: Department of Biochemistry and Molecular Biology, UT MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Ladbury
authors.affiliation: Department of Pathology and Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Andrew Z
authors.initials: AZ
authors.lastname: Fire
authors.affiliation: Department of Genetics, Washington University School of Medicine, Scott Avenue, St. Louis, MO 63110, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Skeath
authors.affiliation: Department of Genetics, UT MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, Houston, TX 77030, USA; Center for Genetics and Genomics, UT MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: sarur@mdanderson.org.
authors.forename: Swathi
authors.initials: S
authors.lastname: Arur
mesh_terms: D000818:Animals; D001483:Base Sequence / Q000502:physiology; D017173:Caenorhabditis elegans / Q000196:embryology / Q000201:enzymology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D009865:Oocytes / Q000378:metabolism*; D009866:Oogenesis / Q000502:physiology; D010766:Phosphorylation; D012330:RNA, Double-Stranded / Q000378:metabolism*; D043244:Ribonuclease III / Q000378:metabolism*
chemical_list: D012330:RNA, Double-Stranded; D043244:Ribonuclease III