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Live or let die: posttranscriptional gene regulation in cell stress and cell death
Marshall P Thomas1, Judy Lieberman
1Program in Cellular and Molecular Medicine, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Abstract:
Studies of the regulation of gene expression historically focused on transcription. However, during stress and apoptosis, profound gene expression changes occur more rapidly and globally than is possible by regulating transcription. Posttranscriptional changes in mRNA processing and translation in response to diverse stresses shut down most protein translation to conserve energy and lead to rapid remodeling of the proteome to promote repair. Pre-mRNA splicing and mRNA stability are fundamentally altered under some stress conditions. Stress pathways coordinate a cytoprotective repair response, while simultaneously initiating signaling that can ultimately trigger cell death. How the cell mediates the decision between repair and apoptosis is largely not understood. In some stresses, microRNAs may tip the balance. Here, we review what is known about posttranscriptional gene regulation during stress, focusing on what is still unknown and how new technologies might be used to understand what changes are most physiologically important in different forms of stress and death.
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