Calcium-induced stabilization of AU-rich short-lived mRNAs is a common default response.
The AU-rich element (AUUUA)n, found in the 3' noncoding region of many short-lived cytokine and proto-oncogene mRNAs, is sufficient to specifically target these mRNAs for rapid degradation in mammalian cells. The mechanism by which the AU-rich element promotes rapid mRNA decay is not known. Previous studies have shown that release of intracellular stored calcium by ionophore treatment of thymocytes and mast cells inhibits the rapid turnover of AU-rich interleukin mRNAs. Increased cytoplasmic half-life of interleukin mRNAs was linked to calcium-induced activation of the N-terminal c-Jun kinase. In this report we have characterized the calcium-induced stabilization of AU-rich mRNAs. We show that calcium induces stabilization of mRNAs with canonical AU-rich elements in all cell types tested. These results indicate that short-lived mRNA stabilization by calcium is not unique to immune cells nor interleukin mRNAs, but is a widespread default response that includes generic AU-rich mRNAs. Stabilization is shown to be rapid but transient, and to act without altering nuclear transcription or cytoplasmic translation rates. These data support the view that calcium release likely stabilizes short-lived mRNAs by altering trans-acting decay factors that promote AU-rich mRNA turnover.
Klein
N
N
Department of Biochemistry and Microbiology, Kaplan Cancer Center, NYU Medical School, New York, NY 10016, USA.
Curatola
A M
AM
Schneider
R J
RJ
D000225:Adenine / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D000001:Calcimycin; D002118:Calcium / Q000378:metabolism*; D002461:Cell Line, Transformed; D006224:Cricetinae; D003593:Cytoplasm; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D007476:Ionophores; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000378:metabolism; D014498:Uracil / Q000378:metabolism
D007476:Ionophores; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D000001:Calcimycin; D014498:Uracil; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000225:Adenine; D002118:Calcium