Early host responses to viral infection rapidly induce an antiviral gene expression program that limits viral replication and recruits sentinel cells of the innate immune system. These responses are mediated by cytokines. The mRNAs that encode cytokines typically harbor destabilizing adenine- and uridine-rich elements (AREs) that direct their constitutive degradation in the cytoplasm. In response to a variety of signals, including viral infection, small pools of cytoplasmic ARE-mRNAs are rapidly stabilized and translated. Thus, mRNA stability plays a key role in antiviral gene expression. Intriguingly, recent studies have identified viral proteins that specifically target ARE-mRNAs for stabilization, suggesting that certain proteins encoded by ARE-mRNAs may be advantageous for infection. Here, we discuss the development of a suite of sensitive and complementary assays to monitor ARE-mRNA turnover. These include luciferase- and destabilized-GFP-based assays that can be adapted for high-throughput screening applications.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ymeth.2011.08.005 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The Conserved CNOT1 Interaction Motif of Tristetraprolin Regulates ARE-mRNA Decay Independently of the p38 MAPK-MK2 Kinase Pathway.
Mol Cell Biol
September 2022
Department of Molecular Biology, School of Biological Sciences, University of California San Diego, La Jolla, California, USA.
The regulation of the mRNA decay activator Tristetraprolin (TTP) by the p38 mitogen-activated protein kinase (MAPK) pathway during the mammalian inflammatory response represents a paradigm for the control of mRNA turnover by signaling. TTP activity is regulated through multiple phosphorylation sites, including an evolutionary conserved serine in its CNOT1 Interacting Motif (CIM) whose phosphorylation disrupts an interaction with CNOT1 of the CCR4-NOT deadenylase complex. Here we present evidence that the TTP CIM recruits the CCR4-NOT deadenylase complex and activates mRNA degradation cooperatively with the conserved tryptophan residues of TTP, previously identified to interact with CNOT9.
View Article and Find Full Text PDFRecruitment of the 4EHP-GYF2 cap-binding complex to tetraproline motifs of tristetraprolin promotes repression and degradation of mRNAs with AU-rich elements.
RNA
March 2016
Division of Biological Sciences, University of California San Diego, La Jolla, California 92093, USA.
The zinc finger protein tristetraprolin (TTP) promotes translation repression and degradation of mRNAs containing AU-rich elements (AREs). Although much attention has been directed toward understanding the decay process and machinery involved, the translation repression role of TTP has remained poorly understood. Here we identify the cap-binding translation repression 4EHP-GYF2 complex as a cofactor of TTP.
View Article and Find Full Text PDFPhysiological networks and disease functions of RNA-binding protein AUF1.
Wiley Interdiscip Rev RNA
March 2015
Alexandria Center for Life Sciences, New York University School of Medicine, New York, NY, USA.
Regulated messenger RNA (mRNA) decay is an essential mechanism that governs proper control of gene expression. In fact, many of the most physiologically potent proteins are encoded by short-lived mRNAs, many of which contain AU-rich elements (AREs) in their 3'-untranslated region (3'-UTR). AREs target mRNAs for post-transcriptional regulation, generally rapid decay, but also stabilization and translation inhibition.
View Article and Find Full Text PDFKaposi's sarcoma-associated herpesvirus G-protein-coupled receptor prevents AU-rich-element-mediated mRNA decay.
J Virol
August 2012
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
During lytic Kaposi's sarcoma-associated herpesvirus (KSHV) infection, host gene expression is severely restricted by a process of global mRNA degradation known as host shutoff, which rededicates translational machinery to the expression of viral proteins. A subset of host mRNAs is spared from shutoff, and a number of these contain cis-acting AU-rich elements (AREs) in their 3' untranslated regions. AREs are found in labile mRNAs encoding cytokines, growth factors, and proto-oncogenes.
View Article and Find Full Text PDFThe role of AUF1 in regulated mRNA decay.
Wiley Interdiscip Rev RNA
March 2012
Department of Molecular Genetics, Microbiology and Immunology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5635, USA.
Messenger ribonucleic acid (mRNA) turnover is a major control point in gene expression. In mammals, many mRNAs encoding inflammatory cytokines, oncoproteins, and G-protein-coupled receptors are destabilized by the presence of AU-rich elements (AREs) in their 3'-untranslated regions. Association of ARE-binding proteins (AUBPs) with these mRNAs promotes rapid mRNA degradation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!