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.
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina, USA.
Oksana
O
Sirenko
Ulrich
U
Böcker
John S
JS
Morris
J Stephen
JS
Haskill
Joanna M
JM
Watson
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