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| Status |
Public on Feb 16, 2018 |
| Title |
RNA-Seq of polysome profiling fractions and whole cell lysates of UVB-irradiated N-TERT keratinocytes |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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 eIF2α (eIF2α-P) protects keratinocytes from UVB-induced apoptosis. In this study, we elucidate the mechanism of eIF2α-P cytoprotection in response to UVB. Loss of eIF2α-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 eIF2α-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 eIF2α-P during stress in a mechanism mediated in part by upstream ORFs situated in the 5’-leader of CDKN1A mRNA. We conclude that eIF2α-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.
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| Overall design |
Untreated and irradiated N-TERT keratinocytes are split into 3 groups: monosome fraction, polysome fraction, and whole cell lysate. N=3.
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| Contributor(s) |
Collier A, Wek R, Spandau D |
| Citation(s) |
29118075 |
| Submission date |
Jun 06, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Ann Collier |
| E-mail(s) |
annie.e.collier@gmail.com
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| Organization name |
Indiana University School of Medicine
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| Street address |
635 N Barnhill Dr MS4067
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| City |
Indianapolis |
| State/province |
IN |
| ZIP/Postal code |
46202 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (18)
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| GSM2651139 |
No Treatment mono, rep1 |
| GSM2651140 |
No Treatment mono, rep2 |
| GSM2651141 |
No Treatment mono, rep3 |
| GSM2651142 |
No Treatment poly, rep1 |
| GSM2651143 |
No Treatment poly, rep2 |
| GSM2651144 |
No Treatment poly, rep3 |
| GSM2651145 |
UVB total, rep1 |
| GSM2651146 |
UVB total, rep2 |
| GSM2651147 |
UVB total, rep3 |
| GSM2651148 |
UVB mono, rep1 |
| GSM2651149 |
UVB mono, rep2 |
| GSM2651150 |
UVB mono, rep3 |
| GSM2651151 |
UVB poly, rep1 |
| GSM2651152 |
UVB poly, rep2 |
| GSM2651153 |
UVB poly, rep3 |
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| Relations |
| BioProject |
PRJNA389466 |
| SRA |
SRP108720 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE99745_Percent_shift_calculations.xlsx |
93.4 Mb |
(ftp)(http) |
XLSX |
| GSE99745_RAW.tar |
11.2 Mb |
(http)(custom) |
TAR (of XLS) |
| GSE99745_Total_RNA_cuffdiff.xlsx |
8.6 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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