ARS2 is required for retinal progenitor cell S-phase progression and Müller glial cell fate specification
Autor: | Oliver A. Krupke, Jennifer Christie, Philip E. B. Nickerson, Minyan Zhu, Monica Mesa-Peres, Perry L. Howard, Bridget C. Ryan, Li-Li Chen, Robert L. Chow, Connor O'Sullivan |
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Rok vydání: | 2020 |
Předmět: |
Cell type
Period (gene) Ependymoglial Cells Cell Biology Biochemistry Retina S Phase Glial cell fate specification Mice 03 medical and health sciences Retinal progenitor 0302 clinical medicine medicine Animals Molecular Biology 030304 developmental biology 0303 health sciences Stem Cells Cell Biology Cell cycle Cell biology DNA-Binding Proteins Phenotype medicine.anatomical_structure sense organs 030217 neurology & neurosurgery Transcription Factors |
Zdroj: | Biochemistry and Cell Biology. 98:50-60 |
ISSN: | 1208-6002 0829-8211 |
Popis: | During a developmental period that extends postnatally in the mouse, proliferating multipotent retinal progenitor cells produce one of 7 major cell types (rod, cone, bipolar, horizontal, amacrine, ganglion, and Müller glial cells) as they exit the cell cycle in consecutive waves. Cell production in the retina is tightly regulated by intrinsic, extrinsic, spatial, and temporal cues, and is coupled to the timing of cell cycle exit. Arsenic-resistance protein 2 (ARS2, also known as SRRT) is a component of the nuclear cap-binding complex involved in RNA Polymerase II transcription, and is required for cell cycle progression. We show that postnatal retinal progenitor cells (RPCs) require ARS2 for proper progression through S phase, and ARS2 disruption leads to early exit from the cell cycle. Furthermore, we observe an increase in the proportion of cells expressing a rod photoreceptor marker, and a loss of Müller glia marker expression, indicating a role for ARS2 in regulating cell fate specification or differentiation. Knockdown of Flice Associated Huge protein (FLASH), which interacts with ARS2 and is required for cell cycle progression and 3′-end processing of replication-dependent histone transcripts, phenocopies ARS2 knockdown. These data implicate ARS2–FLASH-mediated histone mRNA processing in regulating RPC cell cycle kinetics and neuroglial cell fate specification during postnatal retinal development. |
Databáze: | OpenAIRE |
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