PLX115999

GSE99745: RNA-Seq of polysome profiling fractions and whole cell lysates of UVB-irradiated N-TERT keratinocytes

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

In response to UVB irradiation, human keratinocytes transiently block cell cycle progression to allow ample time for DNA repair and cell fate determination. These cellular processes are important for evading the initiation of carcinogenesis in skin. We previously showed that repression of mRNA translation initiation through phosphorylation of eIF2 (eIF2-P) protects keratinocytes from UVB-induced apoptosis. In this study, we elucidate the mechanism of eIF2-P cytoprotection in response to UVB. Loss of eIF2-P induced by UVB diminished G1 arrest, DNA repair rate, and cellular senescence coincident with enhanced cell death in human keratinocytes. Genome-wide translation analyses revealed that the mechanism for these critical changes directed by eIF2-P involved induced expression of CDKN1A encoding p21 protein. p21 is a major regulator of the cell cycle, and we show that human CDKN1A mRNA splice variant 4 is preferentially translated by eIF2-P during stress in a mechanism mediated in part by upstream ORFs situated in the 5-leader of CDKN1A mRNA. We conclude that eIF2-P is cytoprotective in response to UVB by a mechanism featuring translation of a specific splice variant of CDKN1A that facilitates G1 arrest and subsequent DNA repair. SOURCE: Ann Collier (annie.e.collier@gmail.com) - Indiana University School of Medicine