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。     

长链非编码RNA的功能与疾病

长链非编码RNAs（long noncoding RNAs,lncRNAs）是一类长度大于200 nt且不表现出任何蛋白质编码潜能的RNAs,在总非编码RNAs(ncRNA)中占有相当大的比例.对lncRNAs的研究将有助于理解生命体多层次的表达调控网络,并有望为复杂疾病的预测、诊断、和治疗提供新的分子依据.本文在简要介绍lncRNAs的基础上,综合分析了lncRNAs与表观遗传、基因表达调控和疾病发生的关系,以期为进一步的研究提供参考.     

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.     

A novel plant in vitro assay system for pre-mRNA cleavage during 3'-end formation

Messenger RNA (mRNA) maturation in eukaryotic cells requires the formation of the 3' end, which includes two tightly coupled steps: the committing cleavage reaction that requires both correct cis-element signals and cleavage complex formation, and the polyadenylation step that adds a polyadenosine [poly(A)] tract to the newly generated 3' end. An in vitro biochemical assay plays a critical role in studying this process. The lack of such an assay system in plants hampered the study of plant mRNA 3'-end formation for the last two decades. To address this, we have now established and characterized a plant in vitro cleavage assay system, in which nuclear protein extracts from Arabidopsis (Arabidopsis thaliana) suspension cell cultures can accurately cleave different pre-mRNAs at expected in vivo authenticated poly(A) sites. The specific activity is dependent on appropriate cis-elements on the substrate RNA. When complemented by yeast (Saccharomyces cerevisiae) poly(A) polymerase, about 150-nucleotide poly(A) tracts were added specifically to the newly cleaved 3' ends in a cooperative manner. The reconstituted polyadenylation reaction is indicative that authentic cleavage products were generated. Our results not only provide a novel plant pre-mRNA cleavage assay system, but also suggest a cross-kingdom functional complementation of yeast poly(A) polymerase in a plant system.     

Identification of functional lncRNAs in atrial fibrillation by integrative analysis of the lncRNA-mRNA network based on competing endogenous RNAs hypothesis

A mounting body of evidence has suggested that long noncoding RNAs (lncRNAs) play critical roles in human diseases by acting as competing endogenous RNAs (ceRNAs). However, the functions and ceRNA mechanisms of lncRNAs in atrial fibrillation (AF) remain to date unclear. In this study, we constructed an AF-related lncRNA-mRNA network (AFLMN) based on ceRNA theory, by integrating probe reannotation pipeline and microRNA (miRNA)-target regulatory interactions. Two lncRNAs with central topological properties in the AFLMN were first obtained. By using bidirectional hierarchical clustering, we identified two modules containing four lncRNAs, which were significantly enriched in many known pathways of AF. To elucidate the ceRNA interactions in certain disease or normal condition, the dysregulated lncRNA-mRNA crosstalks in AF were further analyzed, and six hub lncRNAs were obtained from the network. Furthermore, random walk analysis of the AFLMN suggested that lncRNA RP11-296O14.3 may function importantly in the pathological process of AF. All these eight lncRNAs that were identified from previous steps (RP11-363E7.4, GAS5, RP11-410L14.2, HAGLR, RP11-421L21.3, RP11-111K18.2, HOTAIRM1, and RP11-296O14.3) exhibited a strong diagnostic power for AF. The results of our study provide new insights into the functional roles and regulatory mechanisms of lncRNAs in AF, and facilitate the discovery of novel diagnostic biomarkers or therapeutic targets.     

Nucleases of the Metallo-β-lactamase Family and Their Role in DNA and RNA Metabolism

ABSTRACT

Proteins of the metallo-β-lactamase family with either demonstrated or predicted nuclease activity have been identified in a number of organisms ranging from bacteria to humans and has been shown to be important constituents of cellular metabolism. Nucleases of this family are believed to utilize a zinc-dependent mechanism in catalysis and function as 5′ to 3′ exonucleases and or endonucleases in such processes as 3′ end processing of RNA precursors, DNA repair, V(D)J recombination, and telomere maintenance. Examples of metallo-β-lactamase nucleases include CPSF-73, a known component of the cleavage/polyadenylation machinery, which functions as the endonuclease in 3′ end formation of both polyadenylated and histone mRNAs, and Artemis that opens DNA hairpins during V(D)J recombination. Mutations in two metallo-β-lactamase nucleases have been implicated in human diseases: tRNase Z required for 3′ processing of tRNA precursors has been linked to the familial form of prostate cancer, whereas inactivation of Artemis causes severe combined immunodeficiency (SCID). There is also a group of as yet uncharacterized proteins of this family in bacteria and archaea that based on sequence similarity to CPSF-73 are predicted to function as nucleases in RNA metabolism. This article reviews the cellular roles of nucleases of the metallo-β-lactamase family and the recent advances in studying these proteins.     

Genome-wide identification and characterization of putative lncRNAs in the diamondback moth, Plutella xylostella (L.)

Long non-coding RNAs (lncRNAs) are of particular interest because of their contributions to many biological processes. Here, we present the genome-wide identification and characterization of putative lncRNAs in a global insect pest, Plutella xylostella. A total of 8096 lncRNAs were identified and classified into three groups. The average length of exons in lncRNAs was longer than that in coding genes and the GC content was lower than that in mRNAs. Most lncRNAs were flanked by canonical splice sites, similar to mRNAs. Expression profiling identified 114 differentially expressed lncRNAs during the DBM development and found that majority were temporally specific. While the biological functions of lncRNAs remain uncharacterized, many are microRNA precursors or competing endogenous RNAs involved in micro-RNA regulatory pathways. This work provides a valuable resource for further studies on molecular bases for development of DBM and lay the foundation for discovery of lncRNA functions in P. xylostella.     

STRUCTURAL CHARACTERIZATION OF THE TERMINAL DOMAINS OF LINEAR PLASMID‐LIKE DNA FROM THE GREEN ALGA ERNODESMIS (CHLOROPHYTA)1

Terminal regions of linear plasmid‐like DNA molecules from chloroplasts of the green alga Ernodesmis verticillata (Kützing) Børgesen were cloned and structurally characterized. Phosphorylation experiments with polynucleotide kinase indicated the presence of a 5′‐phosphate, but the data did not reveal any protective protein(s) at the 5′ end. To characterize the 3′ end of these molecules, homopolymer‐ (poly(G)‐) tailed molecules were annealed to and cloned into a linearized vector that was poly(C) tailed with terminal deoxynucleotidyl transferase. Sequencing analyses verified the heterogeneous nature of the molecules. Two distinct clones displayed extensive terminal inverted repeats (TIRs) at the 3′ end (94 and 433 nt). Shorter TIRs (3–6 nt) were identified at the 3′ end of most clones, which may serve to protect the ends. In fact, exonuclease III and λ exonuclease digested the plasmid‐like DNAs only after heat denaturation, signifying that conformational changes due to such treatment potentially make the 3′ and 5′ ends (respectively) susceptible to degradation. Multiple tandem and direct repeats were evident near the 3′ ends. A consensus sequence of 18+ nt was discovered in nearly every clone opposite the poly(G) tail, suggesting that this sequence has structural and/or functional significance. Pair‐wise sequence comparisons and the presence of repeats indicated that these novel molecules may be highly recombinant.     

lncRNAs在心血管疾病发生中的作用

长链非编码RNA（long noncoding RNAs, lncRNAs）可以在多个阶段干扰基因表达和信号途径。在心血管系统,内皮表达的lncRNAs,如MALAT1和Tie 1 AS可以调节血管生长和功能。平滑肌细胞和内皮细胞中富含的迁移或分化相关的lncRNAs可调控平滑肌细胞收缩表型。在严重心肌梗塞和心衰时,一些lncRNAs表达水平发生调节,如Novlnc6和Nhrt。还有一些lncRNAs参与调节心肌细胞肥大、线粒体功能和心肌细胞凋亡。本文总结了lncRNA在心血管疾病中的研究进展,期待为更有效的治疗心血管疾病开发新的方向。     

长链非编码RNAs与脑卒中

脑卒中严重影响着患者的生存质量,然而其病理生理机制尚不清晰.研究发现,长链非编码RNAs(long non-coding RNAs,lncRNAs)参与了机体多种生理或病理生理过程.在脑卒中患者或缺血性动物模型中,亦发现数百种异常表达的lncRNAs.因此,本综述主要讲述研究比较清晰并与脑卒中相关的lncRNAs的研究...