Palanichamy Jayanth Kumar, Rao Dinesh S
Department of Pathology and Laboratory Medicine, University of California Los Angeles, CA, USA.
Department of Pathology and Laboratory Medicine, University of California Los Angeles, CA, USA ; Jonsson Comprehensive Cancer Center, University of California Los Angeles, CA, USA ; Broad Stem Cell Research Center, University of California Los Angeles, CA, USA ; Division of Biology, California Institute of Technology Pasadena, CA, USA.
Front Genet. 2014 Mar 18;5:54. doi: 10.3389/fgene.2014.00054. eCollection 2014.
It is now well known that gene expression is intricately regulated inside each cell especially in mammals. There are multiple layers of gene regulation active inside a cell at a given point of time. Gene expression is regulated post-transcriptionally by microRNAs and other factors. Mechanistically, microRNAs are known to bind to the 3' UTR of mRNAs and cause repression of gene expression and the number of known microRNAs continues to increase every day. Dysregulated microRNA signatures in different types of cancer are being uncovered consistently implying their importance in cellular homeostasis. However when studied in isolation in mouse models, clear-cut cellular and molecular mechanisms have been described only for a select few microRNAs. What is the reason behind this discrepancy? Are microRNAs small players in gene regulation helping only to fine tune gene expression? Or are their roles tissue and cell type-specific with single-cell level effects on mRNA expression and microRNA threshold levels? Or does it all come down to the technical limitations of high-throughput techniques, resulting in false positive results? In this review, we will assess the challenges facing the field and potential avenues for resolving the cellular and molecular mechanisms of these small but important regulators of gene expression.
现在众所周知，基因表达在每个细胞内受到复杂的调控，尤其是在哺乳动物中。在给定的时间点，细胞内存在多层活跃的基因调控。基因表达在转录后受到微小RNA和其他因子的调控。从机制上讲，已知微小RNA与信使核糖核酸（mRNA）的3'非翻译区（UTR）结合并导致基因表达的抑制，而且已知微小RNA的数量每天都在不断增加。在不同类型的癌症中，失调的微小RNA特征不断被发现，这意味着它们在细胞内稳态中具有重要意义。然而，在小鼠模型中单独研究时，仅针对少数几种微小RNA描述了明确的细胞和分子机制。这种差异背后的原因是什么？微小RNA是基因调控中的小角色，仅有助于微调基因表达吗？还是它们的作用具有组织和细胞类型特异性，对mRNA表达和微小RNA阈值水平具有单细胞水平的影响？或者这一切都归结于高通量技术的技术局限性，导致假阳性结果？在这篇综述中，我们将评估该领域面临的挑战以及解决这些微小但重要的基因表达调节因子的细胞和分子机制的潜在途径。
