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Molecular and Cellular Biology, August 2004, p. 6773-6787, Vol. 24, No. 15
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.15.6773-6787.2004

Global mRNA Stabilization Preferentially Linked to Translational Repression during the Endoplasmic Reticulum Stress Response

Tomoko Kawai, Jinshui Fan, Krystyna Mazan-Mamczarz, and Myriam Gorospe*

Laboratory of Cellular and Molecular Biology, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224-6825

Received 17 February 2004/ Returned for modification 19 March 2004/ Accepted 14 May 2004

The stability of mRNAs undergoing translation has long been a controversial question. Here, we systematically investigate links between mRNA turnover and translation during the endoplasmic reticulum (ER) stress response, a process during which protein synthesis is potently regulated. cDNA array-based approaches to assess the stability and translational status of each mRNA were devised. First, ER stress-triggered changes in mRNA stability were studied by comparing differences in steady-state mRNA levels with differences in gene transcription. Second, changes in translational status were monitored by studying ER stress-induced shifts in the relative distribution of each mRNA along sucrose gradients. Together, the array-derived data reveal complex links between mRNA stability and translation, with all regulatory groups represented: both stabilized and destabilized mRNAs were found among translationally induced as well as translationally suppressed mRNA collections. Remarkably, however, the subset of stabilized mRNAs was prominently enriched in translationally suppressed transcripts, suggesting that ER stress was capable of causing the stabilization of mRNAs associated with a global reduction in protein synthesis. The cDNA array-based approach described here can be applied to global analyses of mRNA turnover and translation and can serve to investigate subsets of mRNAs subject to joint posttranscriptional control.

* Corresponding author. Mailing address: Box 12, LCMB, NIA-IRP, National Institutes of Health, 5600 Nathan Shock Dr., Baltimore, MD 21224-6825. Phone: (410) 558-8443. Fax: (410) 558-8386. E-mail: myriam-gorospe{at}nih.gov.

Molecular and Cellular Biology, August 2004, p. 6773-6787, Vol. 24, No. 15
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.15.6773-6787.2004




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