IL‐1β transcript stability in monocytes is linked to cytoskeletal reorganization and the availability of mRNA degradation factors

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Abstract
Monocyte extravasation initiates reorganization of the cytoskeleton (CSK) and adhesion‐dependent cytokine gene transcription. The actin CSK is thought to be crucial for compartmentalization and translation of mRNA, many of which contain AU‐rich (ARE) instability motifs in the 3′ untranslated region. We investigated regulation of adhesion‐induced IL‐1β expression by the monocyte CSK. In serum‐free adherent monocytes, the induced IL‐1β mRNA was stable and did not coextract with actin filaments. In contrast, in cells adherent in autologous serum, IL‐1β transcripts were unstable, coextracted with actin filaments and were associated with only transient activation of the mitogen‐activated protein kinases (MAPK). Under both conditions of adherence, the ARE‐binding protein AUF1/hnRNP D was readily extracted in the cytosolic fraction. Electro‐injection with AUF1/hnRNP D modified the actin CSK and, surprisingly, stabilized IL‐1β transcripts. These data suggest that the control of mRNA degradation is linked with changes in the CSK. Mitogen‐activated protein kinase activation or alterations in the availability of mRNA degradation factors may mediate these effects.
Funding Information
  • National Institutes of Health (AI26774)
  • Deutsche Forschungsgemeinschaft (1340/1−1, 1340/2−1)