MicroRNAs and cell differentiation in mammalian development

MicroRNAs (miRNAs) are a group of recently discovered small RNAs produced by the cell using a unique process, involving RNA polymerase II, Microprocessor protein complex, and the RNAase III/Dicer endonuclease complex, and subsequently sequestered in an miRNA ribonucleoprotein complex. The biological functions of miRNAs depend on their ability to silence gene expression, primarily via degradation of the target mRNA and/or translational suppression, mediated by the RNA-induced silencing complex (RISC). First discovered in Caenorhabditis elegans (lin-4), miRNAs have now been identified in a wide array of organisms, including plants, zebrafish, Drosophila, and mammals. The expression of miRNAs in multicellular organisms exhibits spatiotemporal, and tissue- and cell-specificity, suggesting their involvement in tissue morphogenesis and cell differentiation. More than 200 miRNAs have been identified or predicted in mammalian cells. Recent studies have demonstrated the importance of miRNAs in embryonic stem cell differentiation, limb development, adipogenesis, myogenesis, angiogenesis and hematopoiesis, neurogenesis, and epithelial morphogenesis. Overexpression (gain-of-function) and inactivation (loss-of-function) are currently the primary approaches to studying miRNA functions. Another family of small RNAs related to miRNAs is the small interfering RNAs (siRNAs), generated by Dicer from long double-stranded RNAs (dsRNAs), and produced from an induced transgene, a viral intruder, or a rogue genetic element. siRNAs silence genes via either mRNA degradation, using the RISC, or DNA methylation. siRNAs are actively being applied in basic, functional genetic studies, particularly in the generation of gene knockdown animals, as well as in gene knockdown studies of cultured cells. These studies have provided invaluable information on the specific function(s) of individual genes. siRNA technology also presents exciting potential as a therapeutic approach in disease prevention and treatment, as suggested by a recent study targeting apolipoprotein B (ApoB) in primates. Further elucidation of how miRNAs and other small RNAs interact with known and yet-to-be identified gene regulatory pathways in the cell should provide us with a more in-depth understanding of the mechanisms regulating cellular function and differentiation, and facilitate the application of small RNA technology in disease control and treatment.     

microRNAs - powerful repression comes from small RNAs

microRNAs (miRNAs) encode a novel class of small, non-coding RNAs that regulate gene expression post-trancriptionally. miRNAs comprise one of the major non-coding RNA families, whose diverse biological functions and unusual capacity for gene regulation have attracted enormous interests in the RNA world. Over the past 16 years, genetic, biochemical and computational approaches have greatly shaped the growth of the field, leading to the identification of thousands of miRNA genes in nearly all metazoans. The key molecular machinery for miRNA biogenesis and silencing has been identified, yet the precise biochemical and regulatory mechanisms still remain elusive. However, recent findings have shed new light on how miRNAs are generated and how they function to repress gene expression. miRNAs provide a paradigm for endogenous small RNAs that mediate gene silencing at a genome-wide level. The gene silencing mediated by these small RNAs constitutes a major component of gene regulation during various developmental and physiological processes. The accumulating knowledge about their biogenesis and gene silencing mechanism will add a new dimension to our understanding about the complex gene regulatory networks.     

RNA-quality control by the exosome

The exosome complex of 3'-->5' exonucleases is an important component of the RNA-processing machinery in eukaryotes. This complex functions in the accurate processing of nuclear RNA precursors and in the degradation of RNAs in both the nucleus and the cytoplasm. However, it has been unclear how different classes of substrate are distinguished from one another. Recent studies now provide insights into the regulation and structure of the exosome, and they reveal striking similarities between the process of RNA degradation in bacteria and eukaryotes.     

microRNA的调控和被调控

microRNA是一大类长度约22 nt的非编码RNA,可与靶基因的3′-UTR区部分或完全配对结合,进而通过降低靶mRNA的稳定性或抑制翻译而下调目的基因的表达. microRNA不仅参与细胞的增殖、分化、死亡等正常生理过程,而且还与包括癌症在内的诸多病理过程密切相关.microRNA通常位于编码基因的内含子区,主要由RNA聚合酶Ⅱ催化而转录为初始microRNA,接着经过一系列的核内、胞浆内酶切步骤而组装成有功能的RNA诱导的沉默复合体.本文将在简要介绍microRNA生物合成和调控功能的基础上,重点综述microRNA被调控的研究进展,主要包括表观遗传学水平、转录水平、转录后水平和降解的调控.近年来的研究,逐步丰富甚至推翻了以往对microRNA的认识,体现了microRNA生物学的复杂性.可以预见,随着研究的深入,microRNA将在疾病的早期防治中发挥越来越重要的作用.     

Key players in regulatory RNA realm of bacteria

Precise regulation of gene expression is crucial for living cells to adapt for survival in diverse environmental conditions. Among the common cellular regulatory mechanisms, RNA-based regulators play a key role in all domains of life. Discovery of regulatory RNAs have made a paradigm shift in molecular biology as many regulatory functions of RNA have been identified beyond its canonical roles as messenger, ribosomal and transfer RNA. In the complex regulatory RNA network, riboswitches, small RNAs, and RNA thermometers can be identified as some of the key players. Herein, we review the discovery, mechanism, and potential therapeutic use of these classes of regulatory RNAs mainly found in bacteria. Being highly adaptive organisms that inhabit a broad range of ecological niches, bacteria have adopted tight and rapid-responding gene regulation mechanisms. This review aims to highlight how bacteria utilize versatile RNA structures and sequences to build a sophisticated gene regulation network.     

Regulation of gene expression by effectors that bind to RNA

Recent studies have revealed several genetic systems in bacteria that use complex RNA structural elements to monitor regulatory signals and control expression of downstream genes. These include RNA thermosensors, in which an inhibitory structure melts at high temperature, and systems where binding of small RNAs or cellular metabolites modulates the structure of the RNA. The remarkable feature of these systems is the ability of the regulatory RNA elements to specifically sense the regulatory signal, without accessory components, and convey that information to the gene expression machinery via a structural change in the nascent RNA.     

CircRNA: a rising star in plant biology

Circular RNAs (circRNAs) are covalently closed single-stranded RNA molecules, which are widespread in eukaryotic cells. As regulatory molecules, circRNAs have various functions, such as regulating gene expression, binding miRNAs or proteins, and being translated into proteins, which are important for cell proliferation and cell differentiation, individual growth and development, as well as many other biological processes. However, compared with that in animal models, studies of circRNAs in plants lags behind and, particularly, the regulatory mechanisms of biogenesis and molecular functions of plant circRNAs remain elusive. Recent studies have shown that circRNAs are wide spread in plants with tissue- or development-specific expression patterns and are responsive to a variety of environmental stresses. In this review, we summarize these advances, focusing on the regulatory mechanisms of biogenesis, molecular and biological functions of circRNAs, and the methods for investigating circRNAs. We also discuss the challenges and the prospects of plant circRNA studies.