Control of cytokine mRNA expression by RNA-binding proteins and microRNAs.
Cytokines are critical mediators of inflammation and host defenses. Regulation of cytokines can occur at various stages of gene expression, including transcription, mRNA export, and post- transcriptional and translational levels. Among these modes of regulation, post-transcriptional regulation has been shown to play a vital role in controlling the expression of cytokines by modulating mRNA stability. The stability of cytokine mRNAs, including TNFα, IL-6, and IL-8, has been reported to be altered by the presence of AU-rich elements (AREs) located in the 3'-untranslated regions (3'UTRs) of the mRNAs. Numerous RNA-binding proteins and microRNAs bind to these 3'UTRs to regulate the stability and/or translation of the mRNAs. Thus, this paper describes the cooperative function between RNA-binding proteins and miRNAs and how they regulate AU-rich elements containing cytokine mRNA stability/degradation and translation. These mRNA control mechanisms can potentially influence inflammation as it relates to oral biology, including periodontal diseases and oral pharyngeal cancer progression.
Department of Craniofacial Biology, Medical University of South Carolina, Charleston, SC, USA.
V
V
Palanisamy
A
A
Jakymiw
E A
EA
Van Tubergen
N J
NJ
D'Silva
K L
KL
Kirkwood
D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation; D007249:Inflammation / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
D020413:3' Untranslated Regions; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D035683:MicroRNAs; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D038621:Regulatory Sequences, Ribonucleic Acid; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2