Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs

The recent discovery that the human and other mammalian genomes produce thousands of long non-coding RNAs (lncRNAs) raises many fascinating questions. These mRNA-like molecules, which lack significant protein-coding capacity, have been implicated in a wide range of biological functions through diverse and as yet poorly understood molecular mechanisms. Despite some recent insights into how lncRNAs function in such diverse cellular processes as regulation of gene expression and assembly of cellular structures, by and large, the key questions regarding lncRNA mechanisms remain to be answered. In this review, we discuss recent advances in understanding the biology of lncRNAs and propose avenues of investigation that may lead to fundamental new insights into their functions and mechanisms of action. Finally, as numerous lncRNAs are dysregulated in human diseases and disorders, we also discuss potential roles for these molecules in human health.     

植物中lncRNAs的研究进展

随着高通量测序技术的飞速发展,越来越多的lncRNAs在植物中被发现,并具有生物学功能。lncRNAs是长度大于200个核苷酸且不具备编码蛋白质功能的一类RNA分子。目前lncRNAs在动物中的功能、作用机制等方面的研究较深入,lncRNAs不仅在表观遗传水平、转录水平、转录后水平上调控基因的表达,也参与诸多生命过程调控如基因组印迹、染色体重塑、转录激活等。在植物中虽有关于lncRNAs的研究,但由于缺乏有效的技术方法而相对滞后。该文就近几年来国内外关于植物lncRNAs的来源、结构特征、分类、功能等方面的研究进展进行综述,为进一步理解和研究植物中lncRNAs的功能和分子机制提供参考。     

植物长链非编码RNA研究进展

长链非编码RNA(Long non-coding RNA,lncRNA)长度大于200个核苷酸,大量存在于生物体中并具有多种生物学功能。目前,植物中发现的lncRNA大多由RNA聚合酶Ⅱ转录,并通过目标模仿、转录干扰、组蛋白甲基化和DNA甲基化等多种机制介导基因的表达,在植物开花、雄性不育、营养代谢、生物和非生物胁迫等生物过程中起着调节因子的作用。文章综述了近年来发现的植物lncRNA数据库、预测方法、表达及可能的生物学功能。     

长链非编码RNA在神经系统发育及神经性疾病中的作用

长链非编码RNA(long non-coding RNA,lncRNA)是一类转录本长度在200至数千个核苷酸序列,且不具有蛋白质编码潜能的非编码RNA。相较于研究较多的微小RNA（microRNA,miRNA）和干扰小RNA（small interfering,siRNA）等非编码小RNA,lncRNA的许多功能仍尚不清楚。但越来越多的研究发现,lncRNA可通过多种方式调控中枢神经系统发育,包括表观遗传组蛋白甲基化、转录辅因子调控、可变剪接调控等途经。而以上途经的异常均与多种人类重大疾病的发生密切相关,例如,阿尔兹海默症（Alzheimer’s disease,AD）、自闭症（autism spectrum disorder,ASD）、精神分裂症（schizophrenia,SZ）等。本文就lncRNA在表观遗传水平、转录水平、转录后水平和翻译水平上调控神经系统发育以及其在人类神经性疾病中的作用进行综述。     

Long non-coding RNAs in hematological malignancies: translating basic techniques into diagnostic and therapeutic strategies

Recent studies have revealed that non-coding regions comprise the vast majority of the human genome and long non-coding RNAs (lncRNAs) are a diverse class of non-coding RNAs that has been implicated in a variety of biological processes. Abnormal expression of lncRNAs has also been linked to different human diseases including cancers, yet the regulatory mechanisms and functional effects of lncRNAs are still ambiguous, and the molecular details also need to be confirmed. Unlike protein-coding gene, it is much more challenging to unravel the roles of lncRNAs owing to their unique and complex features such as functional diversity and low conservation among species, which greatly hamper their experimental characterization. In this review, we summarize and discuss both conventional and advanced approaches for the identification and functional characterization of lncRNAs related to hematological malignancies. In particular, the utility and advancement of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system as gene-editing tools are envisioned to facilitate the molecular dissection of lncRNAs via different knock-in/out strategies. Besides experimental considerations specific to lncRNAs, the roles of lncRNAs in the pathogenesis and progression of leukemia are also highlighted in the review. We expect that these insights may ultimately lead to clinical applications including development of biomarkers and novel therapeutic approaches targeting lncRNAs.     

LncRNA调控骨骼肌发育的分子机制及其在家养动物中的研究进展

骨骼肌是维持机体功能必不可少的组织,与家养动物的产肉率等重要经济性状密切相关。近年来,高通量测序鉴定了大量与骨骼肌生成相关的长链非编码RNA (long non-coding RNA, lncRNA),它们可作为调节因子在表观调控、转录调控以及转录后调控等多个层面调控基因表达。lncRNA通过靶向关键因子参与调控骨骼肌发育的各个环节,包括骨骼肌干细胞增殖、迁移、分化,成肌细胞增殖、分化、肌管融合,肌纤维肥大和纤维类型转换等过程。本文重点归纳了lncRNA在人和小鼠骨骼肌发育中的分子调控机制,介绍了lncRNA的研究方法,综述了lncRNA在家养动物骨骼肌发育中的研究进展,分析了目前家养动物lncRNA研究所面临的困难和挑战,最后展望了未来家养动物lncRNA研究的方向,以期为进一步阐明骨骼肌生长发育的分子调控机制提供参考。     

长链非编码RNA——抗病毒天然免疫应答的新兴调控因子

长链非编码RNA(long non-coding RNAs, lncRNAs)是长度超过200nt的非编码RNA分子的总称。作为一类重要的基因调控因子,lncRNAs在表观遗传学、转录及转录后等多个水平调控靶基因的表达。近年来的研究表明,许多lncRNAs可被病毒或干扰素(interferon, IFN)诱导表达,并作为调控因子在IFN介导的抗病毒天然免疫应答中调节抗病毒相关基因的表达。本文重点阐述了lncRNAs在IFN介导的抗病毒天然免疫应答中的调控作用,尤其是对干扰素刺激基因(interferon-stimulated genes, ISGs)转录的调控作用,并归纳了lncRNAs、IFN和ISGs形成的调控网络,以期为从事lncRNAs调控IFN介导的抗病毒天然免疫应答机制研究的相关科研人员提供参考。     

lncRNA在肿瘤中的表达及作用机制

长链非编码RNA(long non-coding RNAs,lncRNAs)是一类转录本长度大于200 nt,不具有蛋白编码功能的非编码RNA.近年来,随着高通量测序技术的发展,越来越多的功能性lncRNAs逐渐被发现,且已成为研究的热点.研究发现,lncRNAs可以作为致癌或抑癌基因参与肿瘤的发生发展.通过比对肿瘤细胞和正常细胞的表达谱显示,多种lncRNAs在不同类型肿瘤中异常表达.除了表型上的研究,目前已有部分报道深入研究了lncRNAs在肿瘤中的作用机制.例如,lncRNAs与肿瘤细胞凋亡、转移及耐药等过程密切相关.此外,在肿瘤患者的临床常规检验中检测到lncRNAs,提示其能够作为一种潜在的肿瘤诊断和预后因子. lncRNAs有望成为新型肿瘤标志物和肿瘤治疗的靶点,用于诊断、治疗、预测预后.本文将通过对lncRNAs在肿瘤中的作用及其分子机制进行综述.     

nc2Cancer:一个研究与癌症相关人类非编码RNA的数据库

伴随着高通量测序技术的飞速发展,许多新型的非编码RNA陆续被发现,比如长链非编码RNA(lncRNA)和环状RNA(Circular RNA)。先前的研究已经表明这些非编码RNA在基因表达调控过程中起着很重要的作用,并且与癌症的发生有着很密切的联系。但是,由于研究者们仍然对它们行使何种功能知之甚少,鉴定这些非编码RNA是否与人类癌症存在密切的相互关系仍然是一个巨大的挑战。为了促进这一领域的研究,这篇文章的作者分析了大规模的RNA相互作用数据,然后建立了数据库nc2Cancer(http://www.bioinfo.tsinghua.edu.cn/nc2Cancer/index.php)。这个数据库的目标便是提供非编码RNA与癌症之间的全面关系。现在,该nc2Cancer数据库包括了三种类型的非编码RNA分子:长链非编码RNA,环状RNA以及由假基因转录而成的RNA。这项研究将有助于研究者更好地去理解非编码RNA的功能以及它们在人类癌症发生过程中所起到的作用。     

MicroRNAs and long non-coding RNAs in pancreatic cancer: From epigenetics to potential clinical applications

MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two relevant classes of non-coding RNAs (ncRNAs) that play a pivotal role in a number of molecular processes through different epigenetic regulatory mechanisms of gene expression. As a matter of fact, the altered expression of these types of RNAs leads to the development and progression of a varied range of multifactorial human diseases. Several recent reports elucidated that miRNA and lncRNAs have been implicated in pancreatic cancer (PC). For instance, dysregulation of such ncRNAs has been found to be associated with chemoresistance, apoptosis, autophagy, cell differentiation, tumor suppression, tumor growth, cancer cell proliferation, migration, and invasion in PC. Moreover, several aberrantly expressed miRNAs and lncRNAs have the potential to be used as biomarkers for accurate PC diagnosis. Additionally, miRNAs and lncRNAs are considered as promising clinical targets for PC. Therefore, in this review, we discuss recent experimental evidence regarding the clinical implications of miRNAs and lncRNAs in the pathophysiology of PC, their future potential, as well as the challenges that have arisen in this field of study in order to drive forward the design of ncRNA-based diagnostics and therapeutics for PC.