title: RONIN Is an Essential Transcriptional Regulator of Genes Required for Mitochondrial Function in the Developing Retina.
abstract: A fundamental principle governing organ size and function is the fine balance between cell proliferation and cell differentiation. Here, we identify RONIN (THAP11) as a key transcriptional regulator of retinal progenitor cell (RPC) proliferation. RPC-specific loss of Ronin results in a phenotype strikingly similar to that resulting from the G1- to S-phase arrest and photoreceptor degeneration observed in the Cyclin D1 null mutants. However, we determined that, rather than regulating canonical cell-cycle genes, RONIN regulates a cohort of mitochondrial genes including components of the electron transport chain (ETC), which have been recently implicated as direct regulators of the cell cycle. Coincidentally, with premature cell-cycle exit, Ronin mutants exhibited deficient ETC activity, reduced ATP levels, and increased oxidative stress that we ascribe to specific loss of subunits within complexes I, III, and IV. These data implicate RONIN as a positive regulator of mitochondrial gene expression that coordinates mitochondrial activity and cell-cycle progression.
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: poche@bcm.edu.
authors.forename: Ross A
authors.initials: RA
authors.lastname: Poché
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: College of Optometry, University of Houston, Houston, TX 77004, USA.
authors.forename: Elda M
authors.initials: EM
authors.lastname: Rueda
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Tong
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: McElwee
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Leeyean
authors.initials: L
authors.lastname: Wong
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Hsu
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Marion
authors.initials: M
authors.lastname: Dejosez
authors.affiliation: College of Optometry, University of Houston, Houston, TX 77004, USA.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Burns
authors.affiliation: College of Optometry, University of Houston, Houston, TX 77004, USA; Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, USA; Department of Pharmacology, University of Houston, Houston, TX 77004, USA.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Fox
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA; Texas Heart Institute, Houston, TX 77030, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Martin
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Zwaka
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA; Department of Bioengineering, Rice University, Houston, TX 77005, USA. Electronic address: mdickins@bcm.edu.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Dickinson
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D045222:Electron Transport Chain Complex Proteins / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D045222:Electron Transport Chain Complex Proteins; D012097:Repressor Proteins; C530078:Thap11 protein, mouse; D000255:Adenosine Triphosphate