环形RNA分子揭秘

环形RNA分子是一类不具有5＇末端帽子和3＇末端poly（A）尾巴、并以共价键形成环形结构的非编码RNA分子。利用针对环形结构RNA分子的实验和计算方法,并结合新一代高通量测序,现已在多种细胞内发现了大量环形RNA分子的稳定存在。目前,尽管环形RNA分子的产生机制及其代谢仍然不清楚,但是已有的研究表明环形RNA分子具有调控基因表达的功能。对环形RNA分子的产生机制和功能等的进一步研究,将为人们深入理解生命活动在转录水平的复杂性调控提供重要的分子基础和研究依据。  

环状RNA在慢性病发病中作用机制的研究进展

环状RNA作为一种对基因表达进行精细调节的重要非编码RNA,不仅增加了非编码RNA介导的基因调控网络的复杂度,也加深了疾病发病机制研究的深度.虽然近年来环状RNA的功能研究有了长足的进步,确定了其作为ceRNA能够特异性吸附miRNA,解除相应miRNA 对下游靶mRNA 的抑制作用,此类研究也表明核外环状RNA介导的凋亡活化,增殖抑制和细胞与细胞间的交流在疾病发生发展过程中是至关重要的,但我们对环状RNA的了解还只是冰山一角,特别是病理状态下其作用的具体机制仍然需要我们不断探索.在此,本综述的主要目的是回顾目前关于环状RNA在心血管疾病、中枢神经系统疾病和癌症等慢性病领域的研究,探讨以上慢性病发病过程中环状RNA所起的作用以及展望未来环状RNA在疾病发病机制领域的研究.  

环RNA研究概况

在1976年就已经发现 RNA 可以具有环形形式。但是长期以来对环形 RNA（circRNAs）主要是作为一些特例加以研究。随着高通量 RNA 测序技术以及生物信息学的发展，近几年的研究发现circRNAs 在真核生物中普遍存在，并且具有一定的保守性和细胞特异性。越来越多的证据指明circRNAs不是剪切噪音，而是具有一定生物学功能，可能与一系列调控甚至疾病的发生和发展相关。  

靶向Wnt1的miRNA与circRNA及其靶基因间相互作用的生物信息学分析

为对靶向Wnt1的7种miRNAs进行circRNAs及其靶基因的预测，同时分析其与circRNAs及靶基因间的相互作用，分别采用Starbase及miRWALK软件，对文献报道的靶向Wnt1基因的let-7e、miR-21、miR-34a、miR-122、miR-148a、miR-148b与miR-152等7种miRNAs的circRNAs和对应的靶基因进行生物信息学预测．利用Cytoscape 3.2.1对这7种miRNAs和预测所得到的circRNAs及对应的靶基因进行网络分析．并进一步对预测到的靶基因通过DAVID软件进行通路分析． Starbase软件对这7种不同miRNAs所预测的靶circRNAs的数量分别为58、15、41、20、28、28、28个．分别比较miRWALK中7～9个以上软件共有的miRNAs及其与靶基因的关系，发现CHD7基因是唯一一个在三种不同预测范围内与miR-21、 miR-148a、 miR-148b和miR-152等4种miRNAs相对应的靶基因．CNOT6、NBEA、ZFYVE26与ZDHHC17是在两种不同预测范围内与至少4个miRNAs相对应的靶基因．在7种miRNAs所预测靶基因相关的KEGG信号通路中，7～9个软件以上共有的信号通路为Focal adhesion信号通路、MAPK信号通路、Notch信号通路与TGF-beta信号通路．在MAPK信号通路中DUSP1与MRPS35_hsa_circ_001042 均分别是与miR-21、miR-148a、miR-148b及miR-152等4种miRNAs相互作用的靶基因与circRNA．本研究对靶向Wnt1的miRNAs及其相互作用的circRNAs、靶基因与信号通路等进行了网络分析与预测，为进一步分析它们之间的相互作用奠定了基础．  

Circular RNA profiling reveals chi_circ_0008219 function as microRNA sponges in pre-ovulatory ovarian follicles of goats (Capra hircus)

Circular RNAs (circRNAs) are a new class of non-coding RNAs in animals and are a novel target of non-coding RNA (ncRNA) regulation. The mechanism and function of circRNAs have been reported in some species and tissues. However, there is little available information on the functions of circRNAs in the goat reproductive system. In the present study, we deeply sequenced and analyzed circRNAs through bioinformatics to reveal the expression profiles, and predicted 13,950 circRNAs in the pre-ovulatory ovarian follicles of goats for the first time. Thirty-seven circRNAs were differentially expressed in the Boer goat compared with the Macheng black goat. The chi_circ_0008219 was involved in a vast circRNA-miRNA-mRNA co-expression network. Via a luciferase activity assay, chi_circ_0008219 is observed to sponge to 3 ovarian follicle-related miRNAs. These findings demonstrate that circRNAs have potential effects in the ovarian follicles of ewes and may represent a promising new research field in ovarian follicular development.  

Dysregulated circRNAs in plasma from active tuberculosis patients

Endogenous circular RNAs (circRNAs) have been reported in various diseases. However, their role in active TB remains unknown. The study was aimed to determine plasma circRNA expression profile to characterize potential biomarker and improve our understanding of active TB pathogenesis. CircRNA expression profiles were screened by circRNA microarrays in active TB plasma samples. Dysregulated circRNAs were then verified by qRT‐PCR. CircRNA targets were predicted based on analysis of circRNA‐miRNA‐mRNA interaction. GO and KEGG pathway analyses were used to predict the function of circRNA. ROC curve was calculated to evaluate diagnostic value for active TB. A total of 75 circRNAs were significantly dysregulated in active TB plasma. By further validation, hsa_circRNA_103571 exhibited significant decrease in active TB patients and showed potential interaction with active TB‐related miRNAs such as miR‐29a and miR‐16. Bioinformatics analysis revealed that hsa_circRNA_103571 was primarily involved in ras signalling pathway, regulation of actin cytoskeleton, T‐ and B‐cell receptor signalling pathway. ROC curve analysis suggested that hsa_circRNA_103571 had significant value for active TB diagnosis. Circulating circRNA dysregulation may play a role in active TB pathogenesis. Hsa_circRNA_103571 may be served as a potential biomarker for active TB diagnosis, and hsa_circRNA_103571‐miRNA‐mRNA interaction may provide some novel mechanism for active TB.