title: DDX6 Orchestrates Mammalian Progenitor Function through the mRNA Degradation and Translation Pathways.
abstract: In adult tissues, stem and progenitor cells must balance proliferation and differentiation to maintain homeostasis. How this is done is unclear. Here, we show that the DEAD box RNA helicase, DDX6 is necessary for maintaining adult progenitor cell function. DDX6 loss results in premature differentiation and decreased proliferation of epidermal progenitor cells. To maintain self-renewal, DDX6 associates with YBX1 to bind the stem loops found in the 3' UTRs of regulators of proliferation/self-renewal (CDK1, EZH2) and recruit them to EIF4E to facilitate their translation. To prevent premature differentiation of progenitor cells, DDX6 regulates the 5' UTR of differentiation inducing transcription factor, KLF4 and degrades its transcripts through association with mRNA degradation proteins. Our results demonstrate that progenitor function is maintained by DDX6 complexes through two distinct pathways that include the degradation of differentiation-inducing transcripts and by promoting the translation of self-renewal and proliferation mRNAs.
authors.affiliation: Department of Dermatology, University of California, San Diego, La Jolla, CA 92093-0869, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0869, USA; UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA 92093-0869, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0869, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Arribas-Layton
authors.affiliation: Department of Dermatology, University of California, San Diego, La Jolla, CA 92093-0869, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0869, USA; UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA 92093-0869, USA.
authors.forename: Yifang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0869, USA.
authors.forename: Jens
authors.initials: J
authors.lastname: Lykke-Andersen
authors.affiliation: Department of Dermatology, University of California, San Diego, La Jolla, CA 92093-0869, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0869, USA; UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA 92093-0869, USA. Electronic address: gsen@ucsd.edu.
authors.forename: George L
authors.initials: GL
authors.lastname: Sen
mesh_terms: D000066673:Cell Self Renewal; D002478:Cells, Cultured; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D004817:Epidermis / Q000502:physiology*; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D059370:RNA Folding; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*; D051840:Y-Box-Binding Protein 1 / Q000378:metabolism
chemical_list: D039561:Eukaryotic Initiation Factor-4E; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; C094683:DDX6 protein, human; D053487:DEAD-box RNA Helicases