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首页> 外文期刊>Gene: An International Journal Focusing on Gene Cloning and Gene Structure and Function >Faulty old ideas about translational regulation paved the way for current confusion about how microRNAs function.
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Faulty old ideas about translational regulation paved the way for current confusion about how microRNAs function.

机译:有关翻译调控的错误旧观念为当前有关microRNA功能运作的困惑铺平了道路。

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Despite a recent surge of reports about how microRNAs might regulate translation, the question has not been answered. The proposed mechanisms contradict one another, and none is supported by strong evidence. This review explains some deficiencies in the experiments with microRNAs. Some of the problems are traceable to bad habits carried over from older studies of translational regulation, here illustrated by discussing two models involving mRNA binding proteins. One widely-accepted model, called into doubt by recent findings, is the maskin hypothesis for translational repression of cyclin B1 in Xenopus oocytes. The second dubious model postulates repression of translation of ceruloplasmin by mRNA binding proteins. A big fault in the latter case is reconstructing the imagined mechanism before looking carefully at the real thing--a criticism that applies also to studies with microRNAs. Experiments with microRNAs often employ internal ribosome entry sequences (IRESs) as tools, necessitating brief discussion of that topic. A sensitive new assay reveals that many putative IRESs promote expression of downstream cistrons via splicing rather than internal initiation of translation. Recent claims about the biological importance of IRES-binding proteins--including suggestions that these proteins might serve as targets for cancer therapy--are not supported by any meaningful evidence. The bottom line is that older studies of mRNA binding proteins and putative IRESs have created a confusing picture of translational regulation which is not helpful when trying to understand how microRNAs might work. The obvious biological importance of microRNAs makes it essential to understand how they do what they do. Fresh ways of thinking and looking are needed.
机译:尽管最近有关microRNA可能如何调控翻译的报道激增,但尚未回答该问题。提出的机制相互矛盾,没有任何有力的证据支持。这篇评论解释了microRNA实验中的一些缺陷。其中一些问题可追溯到较旧的翻译调控研究带来的不良习惯,此处通过讨论涉及mRNA结合蛋白的两种模型来说明。一种被广泛接受的模型,被最近的发现所质疑,是一种针对非洲爪蟾卵母细胞中细胞周期蛋白B1的翻译抑制的掩模素假说。第二个可疑模型推测mRNA结合蛋白可抑制铜蓝蛋白的翻译。在后一种情况下的一个大缺点是在仔细观察真实事物之前重建了想象的机制-这种批评也适用于microRNA研究。使用microRNA进行的实验通常使用内部核糖体进入序列(IRES)作为工具,因此需要对该主题进行简短的讨论。一项灵敏的新检测方法表明,许多推定的IRES通过剪接而非内部翻译起始来促进下游顺反子的表达。最近关于IRES结合蛋白的生物学重要性的主张-包括这些蛋白可能用作癌症治疗靶标的建议-没有任何有意义的证据支持。最重要的是,对mRNA结合蛋白和假定的IRES的较早研究已经产生了令人困惑的翻译调控图谱,这在试图了解microRNA可能如何工作时无济于事。 microRNA具有明显的生物学重要性,因此必须了解它们的工作方式。需要新的思维方式和外观。

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