长链非编码RNA研究进展

基因组计划研究表明, 在组成人类基因组的30亿个碱基对中, 仅有1.5%的核酸序列用于蛋白质编码, 其余98.5%的基因组为非蛋白质编码序列。这些序列曾被认为是在进化过程中累积的“垃圾序列”而未予以关注, 但在随后启动的ENCODE研究计划中却发现, 75%的基因组序列能够被转录成RNA, 其中近74%的转录产物为非编码RNA(Non-coding RNA, ncRNA)。在非编码RNA中, 绝大多数转录本的长度大于200个碱基, 这些“长链非编码RNA(Long non-coding RNA, lncRNA)”能够在转录及转录后水平上调节蛋白编码基因的表达, 从而广泛地参与包括细胞分化、个体发育在内的重要生命过程, 其异常表达还与多种人类重大疾病的发生密切相关。文章综述了长链非编码RNA的发现、分类、表达、作用机制以及其在个体发育和人类疾病中的作用。     

长非编码RNA在基因调控和肿瘤形成中的作用

哺乳动物中,只有小部分基因转录成为编码蛋白质的RNA,大量的基因则转录为不能编码蛋白质的RNA,即ncRNA。长非 编码RNA(lncRNAs)是分子长度在200-100000 nt 之间的一类ncRNA。lncRNAs 的数量超过蛋白质编码基因的数量。目前,对长非 编码RNA(lncRNAs)的生物学特性,转录调控以及其在肿瘤发生发展中的作用机制的研究任然是RNA研究的热点。lncRNAs 通 过控制染色质重塑,转录调控和录转录后调控而在基因的转录调节中发挥了重要作用。lncRNAs 与多种肿瘤相关,并且在抑制因 素和促进因素中都具有重要的作用。众多文献报道的结果表明lncRNAs 参与调控基因表达,在正常细胞与肿瘤细胞的转换中起 到至关重要的作用。     

长链非编码RNA生物学功能及其意义研究进展

人类基因组DNA核苷酸序列中约93%能被转录为RNA,其中仅2%的转录产物被翻译为蛋白质,余下98%属于非编码RNA（non-coding RNA,ncRNA）。ncRNA中长度超过200 nt的称为长链非编码RNA（long non-coding RNA,LncRNA）,长期以来LncRNA被认为是转录过程中的副产物而不具有生物学功能。近年随着微小RNA（microRNA,miRNA）的研究进展,揭示了ncRNA在人类基因转录后调节、细胞生长、分化、增殖中起着相当重要的作用。同时也提示,相比miRNA,在细胞内转录比例更高的LncRNA具有极其复杂而重要的生物学功能,并与人类疾病密切相关。结合LncRNA的表观遗传学功能及其病理生理意义作一简述。     

Melatonin promotes Cashmere goat (Capra hircus) secondary hair follicle growth: a view from integrated analysis of long non-coding and coding RNAs

The role of melatonin in promoting the yield of Cashmere goat wool has been demonstrated for decades though there remains a lack of knowledge regarding melatonin mediated hair follicle growth. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are widely transcribed in the genome and play ubiquitous roles in regulating biological processes. However, the role of lncRNAs in regulating melatonin mediated hair follicle growth remains unclear. In this study, we established an in vitro Cashmere goat secondary hair follicle culture system, and demonstrated that 500 ng/L melatonin exposure promoted hair follicle fiber growth. Based on long intergenic RNA sequencing, we demonstrated that melatonin promoted hair follicle elongation via regulating genes involved in focal adhesion and extracellular matrix receptor pathways and further cis predicting of lncRNAs targeted genes indicated that melatonin mediated lncRNAs mainly targeted vascular smooth muscle contraction and signaling pathways regulating the pluripotency of stem cells. We proposed that melatonin exposure not only perturbed key signals secreted from hair follicle stem cells to regulate hair follicle development, but also mediated lncRNAs mainly targeted to pathways involved in the microvascular system and extracellular matrix, which constitute the highly orchestrated microenvironment for hair follicle stem cell. Taken together, our findings here provide a profound view of lncRNAs in regulating Cashmere goat hair follicle circadian rhythms and broaden our knowledge on melatonin mediated hair follicle morphological changes.     

植物长链非编码RNA的生物信息学预测与分析研究进展

长链非编码RNA(Long non-coding RNAs,lncRNAs)是一类广泛存在于真核生物中,长度大于200个核苷酸、无蛋白编码功能,具有调控基因转录后表达的RNA转录本。新近研究表明,lncRNA在多种生物途径中起着重要调节作用。生物信息学由生物、数学、计算机科学,统计学等多学科交叉产生,能从全局和系统水平对大数据信息进行深入挖掘与分析。采用生物信息学方法预测与分析lncRNA是当前发现和鉴定植物lncRNA的重要策略之一。本文梳理和总结了近年来采用生物信息学预测植物lncRNA及其靶基因的方法策略,以期为今后深入认知植物lncRNA在植物的生长发育过程、抗逆境胁迫及系统进化等过程中的作用研究提供一定参考。     

The emerging roles of long non-coding RNAs in polyglutamine diseases

Polyglutamine (polyQ) diseases are characterized by trinucleotide repeat amplifications within genes, thus resulting in the formation of polyQ peptides, selective neuronal degeneration and possibly death due to neurodegenerative diseases (NDDs). Long non-coding RNAs (lncRNAs), which exceed 200 nucleotides in length, have been shown to play important roles in several pathological processes of NDDs, including polyQ diseases. Some lncRNAs have been consistently identified to be specific to polyQ diseases, and circulating lncRNAs are among the most promising novel candidates in the search for non-invasive biomarkers for the diagnosis and prognosis of polyQ diseases. In this review, we describe the emerging roles of lncRNAs in polyQ diseases and provide an overview of the general biology of lncRNAs, their implications in pathophysiology and their potential roles as future biomarkers and applications for therapy.     

Genome-wide analysis of long non-coding RNAs in Pichia pastoris during stress by RNA sequencing

Long non-coding RNAs play significant roles in many biological processes. The roles of lncRNAs in Pichia pastoris remain unclear. In this work, we focused on the identification of lncRNAs in P. pastoris and exploration of their potential roles in stress response to PLA₂ overexpression and methanol induction. By strand specific RNA sequencing, 208 novel long non-coding RNAs were identified and analyzed. Bioinformatic analysis showed potential trans-target genes and cis-regulated genes of 39 differential lncRNAs. Functional annotation and sequence motif analysis indicated that lncRNAs participate in pathways related to methanol degradation and production of the recombinant protein. The differential expression of lncRNAs was validated by qRT-PCR. Lastly, the potential functions of three lncRNAs were evaluated by knockdown of their expression and analysis of the expression levels of target genes. Our study identifies novel lncRNAs in P. pastoris induced during use as a bioreactor, facilitating future functional research.     

牵张应力刺激介导间充质干细胞的信使RNA和长链非编码RNA表达谱变化

目的探讨信使RNA和长链非编码RNA在牵张应力刺激间充质干细胞（MSC）成骨分化中的作用。 方法分离培养正常人骨髓MSC,分为应力组与无应力组,应力组通过FlexCell应力系统对其施加外源性应力（5﹪形变、频率0.1 Hz、作用时间4 h/d）,无应力组不予以外源性应力刺激,通过茜素红实验和碱性磷酸酶实验检测其成骨分化能力改变。提取应力刺激下第7天RNA,进行全基因组及长链非编码芯片表达谱检测,通过生物信息学方法分析和鉴定关键长链非编码RNA。采用两样本t检验进行统计学分析。 结果成骨第14天应力组MSC茜素红定量OD值为1.46±0.19,高于无应力组MSC 0.62±0.08,差异具有统计学意义（t?= -1.99,P < 0.05）。此外,成骨第14天应力组MSC碱性磷酸酶结果（265.3±31.2）U/L,较无应力组（121.2±21.2）U/L升高（t = -12.23,P < 0.05）。通过芯片表达谱检测,牵张应力刺激下成骨第7天共有差异表达信使RNA 598个,差异表达长链非编码RNA 329个。通过KEGG分析提示WNT信号通路是差异表达最明显的信号通路,其中WNT5a表达变化最为明显（6.74倍,P?< 0.01）。通过共表达分析提示lnc-RNA-SSR是调控WNT5a表达的主要长链非编码RNA。 结论牵张应力刺激下MSC的信使RNA和长链非编码RNA表达谱明显改变,其中lnc-RNA-SSR可能通过WNT5a影响MSC成骨分化能力。     

High expression of long non-coding RNA H19 is required for efficient tumorigenesis induced by Bcr-Abl oncogene

Dysregulation of non-coding RNA H19 has been observed in various tumors. However, it remains unknown whether H19 is involved in Bcr-Abl-induced leukemia. Here, we demonstrate a critical requirement for H19 in Bcr-Abl-mediated tumorigenesis. H19 was highly expressed in Bcr-Abl-transformed cell lines and primary cells derived from patients in a Bcr-Abl kinase-dependent manner. Silencing H19 expression sensitized leukemic cells to undergo imatinib-induced apoptosis and inhibited Bcr-Abl-induced tumor growth. Furthermore, H19 was shown to be regulated by c-Myc in Bcr-Abl-expressing cells. These results reveal an important role H19 plays in Bcr-Abl-mediated transformation and provide novel insights into complex mechanisms underlying Bcr-Abl-induced cancers.     

Screening and bioinformatics analysis of mRNA,long non-coding RNA and circular RNA expression profiles in mucoepidermoid carcinoma of salivary gland

Mucoepidermoid carcinoma (MEC) of salivary gland is a disease characterized by high rate of diatant metastasis, and associated with poor outcomes. However, the molecular mechanisms underlying the MEC remain poorly understand. Here, we simultaneously detected, for the first time, the expression profiles of mRNAs, lncRNAs, and circRNAs in four pairs of MEC and matched non-carcinoma tissues by microarrays. A total of 3612?mRNA, 3091 lncRNAs, and 284 circRNAs were altered during the pathogenesis of MEC. The functions of these differentially expressed RNAs were predicted by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Co-expression networks of lncRNA-mRNA and circRNA-miRNA were conducted to uncovered the hidden ceRNA mechanisms. Moreover, NONHSAT154433.1 that associated with ADAM12 and hsa_circ_0012342 were further screened and confirmed using qRT-PCR analysis. In conclusion, this study provides a systematic perspective on the potential function of non-coding RNAs (ncRNAs) in the molecular mechanisms of MEC. Among these, NONHSAT154433.1 and hsa_circ_0012342 might be served as potential prognostic biomarkers and therapeutic target of MEC.     

Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease

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链球菌非编码小RNA研究进展

非编码小RNA(Small non-coding RNA,sRNA)是一种存在于原核和真核生物中的新型调控RNA,长度约为40～500个核苷酸。作为一类关键的调控因子,sRNA通过与靶mRNA或蛋白质结合来调控细胞内的基因表达。大部分细菌sRNA在大肠杆菌等革兰氏阴性菌中被发现并研究,但近十年来越来越多的sRNA在革兰氏阳性菌中被逐步发现。作为一类革兰氏阳性菌,链球菌属中sRNA目前研究主要集中在毒力调节,鲜有其他调控的报道。本文总结了链球菌中sRNA的最新进展,并介绍其主要功能和机理,以期为细菌sRNA研究提供借鉴。     

植物非编码RNA调控春化作用的表观遗传

在自然界中许多高等植物需要通过冬季的低温阶段实现从营养生长到生殖生长的时期转化,这一生物学过程称作春化作用。小麦(Triticum aestivum L.)和油菜(Brassica napus L.)等作物以种子为产品器官,生产上往往通过茬口安排和栽培措施使植株尽早通过春化作用,以促进花芽形成和花器官发育,而大白菜(B rapa ssp.pekinenesis)和甘蓝(B.oleracea)等作物以叶球等营养器官作为产品器官,生产上则设法避免低温引起的春化作用,以保证产品器官的充分生长。FLOWERING LOCUS C(FLC)作为一种重要的开花抑制蛋白负调控春化作用,参与植株从营养生长向生殖生长的转化过程。文章综述了春化中FLC表达受抑制主要通过低温诱导表达FLC基因区域的非编码RNA以及VRN1、VRN2、VIN3等蛋白参与介导组蛋白甲基化,从而在表观遗传上控制春化作用的进程和产品器官的正常发育。