RNA開(kāi)關(guān)或核糖開(kāi)關(guān)(涉及小配體向RNA上的結(jié)合)已知在細(xì)菌、真菌和植物中調(diào)控基因表達(dá),,在那里它們對(duì)各種不同的代謝物或營(yíng)養(yǎng)物的缺乏或過(guò)多頻繁做出反應(yīng),。
現(xiàn)在,一種RNA開(kāi)關(guān)已在人類細(xì)胞中被發(fā)現(xiàn),。它是編碼“血管內(nèi)皮細(xì)胞生長(zhǎng)因子”(VEGF)的mRNA的3′未轉(zhuǎn)譯區(qū)域的一個(gè)成分,,而VEGF則是對(duì)血管形成非常關(guān)鍵的一種蛋白??砷_(kāi)關(guān)的mRNA可結(jié)合兩種不同的復(fù)合物:GAIT 或 hnRNP L,。其中一種的結(jié)合誘導(dǎo)產(chǎn)生一個(gè)特定的構(gòu)形,它會(huì)阻止另一種的結(jié)合,。具體結(jié)合哪個(gè)因子,,取決于指示炎癥和缺氧狀態(tài)的環(huán)境信號(hào)。該開(kāi)關(guān)的形成可能是為了維持對(duì)缺氧或發(fā)炎組織的氧供應(yīng),,并且可能是在多細(xì)胞動(dòng)物中調(diào)控基因表達(dá)的一種依賴于蛋白的RNA開(kāi)關(guān)的例子(在這些動(dòng)物體內(nèi),,對(duì)不同輸入信號(hào)的精確集成要比迅速反應(yīng)更為重要)。(生物谷Bioon.com)
生物谷推薦原始出處:
Nature 457, 915-919 (12 February 2009) | doi:10.1038/nature07598
A stress-responsive RNA switch regulates VEGFA expression
Partho Sarothi Ray1,2, Jie Jia1, Peng Yao1, Mithu Majumder3, Maria Hatzoglou3 & Paul L. Fox1
1 Department of Cell Biology, The Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
2 Department of Biology, Indian Institute of Science Education and Research, Kolkata 700106, India
3 Department of Nutrition, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA
Ligand binding to structural elements in the non-coding regions of messenger RNA modulates gene expression1, 2. Ligands such as free metabolites or other small molecules directly bind and induce conformational changes in regulatory RNA elements known as riboswitches1, 2, 3, 4. 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 system5, or protein-bound metabolites in the glucose- or amino-acid-stimulated terminator-anti-terminator systems6, 7. All of these switch types are found in bacteria, fungi and plants8, 9, 10. 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)-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--activated inhibitor of translation complex11, 12 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.