|
Status |
Public on Jan 05, 2011 |
Title |
ATM regulates a DNA damage response post-transcriptional RNA operon in lymphocytes |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
|
Summary |
Maintenance of genomic stability depends on the DNA damage response (DDR), a biological barrier in early stages of cancer development. Failure of this response results in genomic instability and high predisposition toward lymphoma, as seen in patients with ataxia-telangiectasia mutated (ATM) dysfunction. ATM activates multiple cell cycle checkpoints and DNA repair following DNA damage, but its influence on posttranscriptional gene expression has not been examined on a global level. We show that ionizing radiation (IR) modulates the dynamic association of the RNA-binding protein HuR with target mRNAs in an ATM-dependent manner, potentially coordinating the genotoxic response as an RNA operon. Pharmacologic ATM inhibition and use of ATM-null cells revealed a critical role for ATM in this process. Numerous mRNAs encoding cancer-related proteins were differentially associated with HuR depending on the functional state of ATM, in turn affecting expression of encoded proteins. The findings presented here reveal a previously unidentified role of ATM in controlling gene expression post-transcriptionally. Dysregulation of this DDR RNA operon is likely relevant to lymphoma development in ataxia-telangiectasia individuals. These novel RNA regulatory modules and genetic networks provide critical insight into the function of ATM in oncogenesis.
|
|
|
Overall design |
B-lymphocyte cell lines GM02184 (wild type, ATM +/+) and GM03332 (AT, ATM -/-) were either untreated or exposed to 1 Gy of IR. 6 h later cells were harvested and used for immunoprecipitation (IP) in the presence of HuR antibody (Santa Cruz Biotech.). RNA from IP material was extracted and used for microarray analysis.
|
|
|
Contributor(s) |
Mazan-Mamczarz K, Hagner PR, Zhang Y, Dai B, Lehrmann E, Becker KG, Keene JD, Gorospe M, Liu Z, Gartenhaus RB |
Citation(s) |
21209379 |
Submission date |
Dec 03, 2010 |
Last update date |
Jun 22, 2020 |
Contact name |
Supriyo De |
Organization name |
NIA-IRP, NIH
|
Department |
Laboratory of Genetics and Genomics
|
Lab |
Computational Biology & Genomics Core
|
Street address |
251 Bayview Blvd
|
City |
Baltimore |
State/province |
Maryland |
ZIP/Postal code |
21224 |
Country |
USA |
|
|
Platforms (1) |
GPL6947 |
Illumina HumanHT-12 V3.0 expression beadchip |
|
Samples (12)
|
|
Relations |
BioProject |
PRJNA135585 |