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Cell Rep. 2016 Feb 23;14(7):1684-1697. doi: 10.1016/j.celrep.2016.01.039. Epub 2016 Feb 11.

RONIN Is an Essential Transcriptional Regulator of Genes Required for Mitochondrial Function in the Developing Retina.

Author information

1
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.
2
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.
3
College of Optometry, University of Houston, Houston, TX 77004, USA.
4
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.
5
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.
6
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.
7
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.

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.

PMID:
26876175
PMCID:
PMC4767647
DOI:
10.1016/j.celrep.2016.01.039
[Indexed for MEDLINE]
Free PMC Article

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