title: DICER1: mutations, microRNAs and mechanisms.
abstract: Dicer is central to microRNA-mediated silencing and several other RNA interference phenomena that are profoundly embedded in cancer gene networks. Most recently, both germline and somatic mutations in DICER1 have been identified in diverse types of cancer. Although some of the mutations clearly reduce the dosage of this key enzyme, others dictate surprisingly specific changes in select classes of small RNAs. This Review reflects on the molecular properties of the Dicer enzymes in small RNA silencing pathways, and rationalizes the newly discovered mutations on the basis of the activities and functions of its determinants.
authors.affiliation: 1] Departments of Human Genetics, Medicine and Oncology, McGill University; Lady Davis Institute, Jewish General Hospital and Research Institute, McGill University Health Centre, Montreal, Quebec, Canada. [2].
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
authors.affiliation: 1] [2].
authors.forename: John R
authors.initials: JR
authors.lastname: Priest
authors.affiliation: 1] Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada, H3A 1A3. [2].
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Duchaine
mesh_terms: D000818:Animals; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D043244:Ribonuclease III / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D035683:MicroRNAs; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases