Publication Date:
2008-12-23
Description:
Ligand binding to structural elements in the non-coding regions of messenger RNA modulates gene expression. Ligands such as free metabolites or other small molecules directly bind and induce conformational changes in regulatory RNA elements known as riboswitches. Other types of RNA switches are activated by complexed metabolites-for example, RNA-ligated metabolites such as aminoacyl-charged transfer RNA in the T-box system, or protein-bound metabolites in the glucose- or amino-acid-stimulated terminator-anti-terminator systems. All of these switch types are found in bacteria, fungi and plants. Here we report an RNA switch in human vascular endothelial growth factor-A (VEGFA, also known as VEGF) mRNA 3' untranslated region (UTR) that integrates signals from interferon (IFN)-gamma and hypoxia to regulate VEGFA translation in myeloid cells. Analogous to riboswitches, the VEGFA 3' UTR undergoes a binary conformational change in response to environmental signals. However, the VEGFA 3' UTR switch is metabolite-independent, and the conformational change is dictated by mutually exclusive, stimulus-dependent binding of proteins, namely, the IFN-gamma-activated inhibitor of translation complex and heterogeneous nuclear ribonucleoprotein L (HNRNPL, also known as hnRNP L). We speculate that the VEGFA switch represents the founding member of a family of signal-mediated, protein-dependent RNA switches that evolved to regulate gene expression in multicellular animals in which the precise integration of disparate inputs may be more important than the rapidity of response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858559/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858559/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ray, Partho Sarothi -- Jia, Jie -- Yao, Peng -- Majumder, Mithu -- Hatzoglou, Maria -- Fox, Paul L -- P01 HL029582/HL/NHLBI NIH HHS/ -- P01 HL029582-26A18735/HL/NHLBI NIH HHS/ -- P01 HL076491/HL/NHLBI NIH HHS/ -- P01 HL076491-050002/HL/NHLBI NIH HHS/ -- P01 HL29582/HL/NHLBI NIH HHS/ -- P01 HL76491/HL/NHLBI NIH HHS/ -- R01 DK053307/DK/NIDDK NIH HHS/ -- R01 DK060596/DK/NIDDK NIH HHS/ -- R01 DK060596-08/DK/NIDDK NIH HHS/ -- R01 DK60596/DK/NIDDK NIH HHS/ -- R01 HL067725/HL/NHLBI NIH HHS/ -- R01 HL067725-04/HL/NHLBI NIH HHS/ -- R01 HL67725/HL/NHLBI NIH HHS/ -- England -- Nature. 2009 Feb 12;457(7231):915-9. doi: 10.1038/nature07598. Epub 2008 Dec 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, The Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19098893" target="_blank"〉PubMed〈/a〉
Keywords:
3' Untranslated Regions
;
Amino Acyl-tRNA Synthetases
;
Anoxia/metabolism
;
*Gene Expression Regulation
;
Gene Silencing
;
Heterogeneous-Nuclear Ribonucleoprotein L/metabolism
;
Humans
;
Interferon-gamma/metabolism
;
Myeloid Cells/metabolism/physiology
;
RNA/chemistry/*metabolism
;
Signal Transduction
;
Stress, Physiological/*physiology
;
U937 Cells
;
Vascular Endothelial Growth Factor A/genetics/*metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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