HuA and tristetraprolin are induced following T cell activation and display distinct but overlapping RNA binding specificities.
AU-rich elements found in the 3'-untranslated regions of cytokine and proto-oncogene transcripts regulate mRNA degradation and function as binding sites for the mRNA-stabilizing protein HuA and the mRNA-destabilizing protein tristetraprolin. Experiments were performed to evaluate the expression of HuA and tristetraprolin in purified human T lymphocytes and to evaluate the ability of these proteins to recognize specific AU-rich sequences. HuA is a predominantly nuclear protein that can also be found in the cytoplasm of resting T lymphocytes. Within 1 h after stimulation of T lymphocytes with anti-T cell receptor antibodies or a combination of a phorbol myristate acetate and ionomycin, an increase in cytoplasmic HuA RNA-binding activity was observed. Although absent in resting cells, cytoplasmic tristetraprolin protein was detected 3-6 h following activation. HuA recognized specific AU-rich sequences found in c-jun or c-myc mRNA that were poorly recognized by tristetraprolin. In contrast, tristetraprolin recognized an AU-rich sequence in interleukin-2 mRNA that was poorly recognized by HuA. Both HuA and tristetraprolin, however, recognized AU-rich sequences from c-fos, interleukin-3, tumor necrosis factor-alpha, and granulocyte/macrophage colony-stimulating factor mRNA. HuA may transiently stabilize a subset of AU-rich element-containing transcripts following T lymphocyte activation, and tristetraprolin may subsequently mediate their degradation.
Raghavan
A
A
Department of Microbiology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Robison
R L
RL
McNabb
J
J
Miller
C R
CR
Williams
D A
DA
Bohjanen
P R
PR
D020413:3' Untranslated Regions; D001483:Base Sequence; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000378:metabolism; D008213:Lymphocyte Activation; D000090063:Proto-Oncogene Mas; D012313:RNA / Q000378:metabolism*; D015347:RNA Probes; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D051816:Tristetraprolin
D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D015347:RNA Probes; D016601:RNA-Binding Proteins; D051816:Tristetraprolin; C497552:ZFP36 protein, human; D012313:RNA