IL-1 beta transcript stability in monocytes is linked to cytoskeletal reorganization and the availability of mRNA degradation factors.
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-1 beta expression by the monocyte CSK. In serum-free adherent monocytes, the induced IL-1 beta mRNA was stable and did not coextract with actin filaments. In contrast, in cells adherent in autologous serum, IL-1 beta 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-1 beta 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.
Sirenko
Oksana
O
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina, USA.
Böcker
Ulrich
U
Morris
John S
JS
Haskill
J Stephen
JS
Watson
Joanna M
JM
D008841:Actin Cytoskeleton / Q000737:chemistry / Q000648:ultrastructure*; D002448:Cell Adhesion; D002478:Cells, Cultured; D003470:Culture Media; D003598:Cytoskeletal Proteins / Q000032:analysis; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000032:analysis; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D007382:Intermediate Filaments / Q000737:chemistry; D007700:Kinetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000648:ultrastructure*; D020871:RNA Stability; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000032:analysis; D015398:Signal Transduction; D014158:Transcription, Genetic
D003470:Culture Media; D003598:Cytoskeletal Proteins; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D007375:Interleukin-1; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D020928:Mitogen-Activated Protein Kinases