Crx Is Posttranscriptionally Regulated by Light Stimulation in Postnatal Rat Retina

Abstract

Cone rod homeobox (Crx) plays a key role at the center of a regulatory network that coordinates many pathways in the retina. Its abnormal expression induces retinal disorders. However, the underlying regulatory mechanism of Crx expression is not well defined. Here, we present data that show that the levels of Crx mRNA were inconsistent with that of Crx protein in primary retinal neurocytes cultured in light conditions. Crx protein levels were significantly higher (2.56-fold) in cells cultured in the dark than in cells cultured in light, whereas Crx mRNA was not changed in either type of cell. Moreover, the expression of Crx protein showed a significant light intensity-dependent decrease. Consistently, Crx downstream genes rhodopsin and arrestin also decreased in retinal neurocytes upon light exposure. Furthermore, Crx promoter activity assay performed in primary retinal neurocytes further indicated that light exposure and darkness did not affect its inducibility. In addition, the inconsistency between Crx mRNA and protein expression after light exposure was not observed in 661w cells transfected with plasmid pcDNA3.1-Crx, suggesting that the inconsistency between Crx mRNA and protein induced by light was specific to the endogenous Crx. More importantly, this observation was confirmed in vivo in postnatal day 15 (P15) retinas but not in adult retinas, further implicating that the posttranscriptional regulation mechanism may be involved in Crx expression in the developing retina. Therefore, our study sheds light on the mechanism of Crx expression in postnatal rat retina.

Paternal genetic effects of cadmium exposure during pregnancy on hormone synthesis disorders in ovarian granulosa cells of offspring

“…We noticed that the mRNA and protein expression levels of some hormone synthesis-related genes are not consistent (e.g., Star, Cyp11a1, etc.). Complex regulatory mechanisms are known to exist during mRNA transcription and protein translation [ 30 , 31 ], and therefore, protein translation regulatory mechanisms may be activated in the F2 generation, allowing protein levels to rise. This is consistent with our previous findings in maternally inheritance models [ 8 ].…”

Association analyses of rare variants identify two genes associated with refractive error

“…Certain mutations in this gene cause several retinal disorders, including cone-rod dystrophy, retinitis pigmentosa, adult-onset macular dystrophy and Leber congenital amaurosis [ 23 , 26 ]. Additionally, the Cone-Rod Homeobox ( CRX ) Transcription Factor regulates the expression of over 700 genes in the retina, including downstream effects over rhodopsin and cone arrestin [ 27 ]. CRX expression in the retinal cells was inhibited by light stimulation, a mechanism previously implicated in myopia development [ 28 , 29 ].…”