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Genomics, Proteomics & Bioinformatics (GPB; ISSN 1672-0229, CN11-4926/Q), a peer-reviewed international journal in English, is sponsored by Beijing Institute of Genomics, Chinese Academy of Sciences and Genetics Society of China, and jointly published by Elsevier and Science Press bi-monthly.

The publications of the journal are high-quality papers from all over the world in the fields of genomics, proteomics, and bioinformatics. For manuscripts submitted to GPB,direct rejection,direct acceptance or further review will be decided within 5 days. Besides, GPB offers Article-in-Press, by which all the accepted manuscripts can be available online ahead of its printed issue print for fast dissemination.


Recent Articles (Volume:15, Issue:3)

1. Epitranscriptomics: Toward A Better Understanding of RNA Modifications

Xushen Xiong, Chengqi Yi, Jinying Peng


Page 147-153

2. The RNA Modification N6-methyladenosine and Its Implications in Human Disease

Pedro J. Batista

Impaired gene regulation lies at the heart of many disorders, including developmental diseases and cancer. Furthermore, the molecular pathways that control gene expression are often the target of cellular parasites, such as viruses. Gene expression is controlled through multiple mechanisms that are coordinated to ensure the proper and timely expression of each gene. Many of these mechanisms target the life cycle of the RNA molecule, from transcription to translation. Recently, another layer of regulation at the RNA level involving RNA modifications has gained renewed interest of the scientific community. The discovery that N6-methyladenosine (m6A), a modification present in mRNAs and long noncoding RNAs, can be removed by the activity of RNA demethylases, launched the field of epitranscriptomics; the study of how RNA function is regulated through the addition or removal of post-transcriptional modifications, similar to strategies used to regulate gene expression at the DNA and protein level. The abundance of RNA post-transcriptional modifications is determined by the activity of writer complexes (methylase) and eraser (RNA demethylase) proteins. Subsequently, the effects of RNA modifications materialize as changes in RNA structure and/or modulation of interactions between the modified RNA and RNA binding proteins or regulatory RNAs. Disruption of these pathways impairs gene expression and cellular function. This review focuses on the links between the RNA modification m6A and its implications in human diseases.
基因表达调控障碍是引起包括发育缺陷、肿瘤等在内的多种疾病的关键因素。而调控基因表达的分子信号通路往往是胞内寄生生物,如病毒等的靶点。基因的表达受到多种机制的共同调控,这些机制协调作用,确保每个基因正确及时的表达。这些机制中很大一部分是通过靶向RNA分子生命周期的转录及翻译的过程来发挥作用。近期,另一层涉及RNA修饰对RNA水平进行调控的新机制重新引起了科学界的兴趣。N6-甲基腺苷(N6-methyladenosine,m6A)修饰存在于信使RNA(mRNAs)和长链非编码RNA(long noncoding RNAs)上,该修饰可被RNA去甲基化酶移除。这一发现开拓了一项新的研究领域——转录组表观遗传学。转录组表观遗传学主要研究RNA转录后修饰如何影响RNA的功能,这与此前研究DNA及蛋白水平调控基因表达的机制类似。RNA转录后修饰水平由“书写器”(RNA甲基化酶)和“擦除器”(RNA去甲基化酶)活性决定。而RNA修饰主要通过改变RNA的结构以及/或调整被修饰RNA与RNA结合蛋白或调节性RNA的相互作用实现其功能。这些信号通路的破坏将会影响基因的表达及细胞的功能。本综述着重介绍RNA修饰m6A与不同人类疾病的关联。

Page 154-163

3. Silencing of Transposable Elements by piRNAs in Drosophila: An Evolutionary Perspective

Shiqi Luo, Jian Lu

Transposable elements (TEs) are DNA sequences that can move within the genome. TEs have greatly shaped the genomes, transcriptomes, and proteomes of the host organisms through a variety of mechanisms. However, TEs generally disrupt genes and destabilize the host genomes, which substantially reduce fitness of the host organisms. Understanding the genomic distribution and evolutionary dynamics of TEs will greatly deepen our understanding of the TE-mediated biological processes. Most TE insertions are highly polymorphic in Drosophila melanogaster, providing us a good system to investigate the evolution of TEs at the population level. Decades of theoretical and experimental studies have well established “transposition-selection” population genetics model, which assumes that the equilibrium between TE replication and purifying selection determines the copy number of TEs in the genome. In the last decade, P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) were demonstrated to be master repressors of TE activities in Drosophila. The discovery of piRNAs revolutionized our understanding of TE repression, because it reveals that the host organisms have evolved an adaptive mechanism to defend against TE invasion. Tremendous progress has been made to understand the molecular mechanisms by which piRNAs repress active TEs, although many details in this process remain to be further explored. The interaction between piRNAs and TEs well explains the molecular mechanisms underlying hybrid dysgenesis for the I-R and P-M systems in Drosophila, which have puzzled evolutionary biologists for decades. The piRNA repression pathway provides us an unparalleled system to study the co-evolutionary process between parasites and host organisms.

Page 164-176

4. Transcriptional and Post-transcriptional Gene Regulation by Long Non-coding RNA

Iain M. Dykes, Costanza Emanueli

Advances in genomics technology over recent years have led to the surprising discovery that the genome is far more pervasively transcribed than was previously appreciated. Much of the newly-discovered transcriptome appears to represent long non-coding RNA (lncRNA), a heterogeneous group of largely uncharacterised transcripts. Understanding the biological function of these molecules represents a major challenge and in this review we discuss some of the progress made to date. One major theme of lncRNA biology seems to be the existence of a network of interactions with microRNA (miRNA) pathways. lncRNA has been shown to act as both a source and an inhibitory regulator of miRNA. At the transcriptional level, a model is emerging whereby lncRNA bridges DNA and protein by binding to chromatin and serving as a scaffold for modifying protein complexes. Such a mechanism can bridge promoters to enhancers or enhancer-like non-coding genes by regulating chromatin looping, as well as conferring specificity on histone modifying complexes by directing them to specific loci.
长非编码RNA(long non-coding RNA, lncRNA)是基因组学技术发展中的重大新发现,它具有高度异质性,但没有描述其功能和特点的转录本,这对理解它的生物学功能和意义带来了巨大的挑战。全基因组关联分析发现这些lncRNA基因富有多态性特征或者疾病相关联的多态性特征。因此,lncRNA的生物学功能研究对其厘清lncRNA本身或其疾病相关性是具有重大意义的。这篇综述整合了目前对lncRNA的研究,全面介绍了它的发现历程、多样性以及主要生物学功能。lncRNA的发现得益于测序技术的发展,由于其本身具有多样性的特点,使得它的生物学功能也具有多样化。lncRNA既可从转录后水平上调控基因表达,也可从转录水平上调控基因表达。在转录后调控机制上,lncRNA可与microRNA(miRNA)通路相互作用形成一个调控网络:lncRNA不仅是miRNA的主要来源,也作为miRNA的负调控因子。在转录调控机制上,lncRNA通过结合核染色质或者作为修饰蛋白复合体的支架来搭建DNA与蛋白质之间的调控桥梁。同时,lncRNA还通过调节核染色质循环以及招募特异性的组蛋白修饰复合物到特定位点的方式来搭建启动子到增强子或增强子相似非编码基因之间的调控桥梁。

Page 177-186

5. Primate-specific Long Non-coding RNAs and MicroRNAs

Hassaan Mehboob Awan, Abdullah Shah, Farooq Rashid, Ge Shan

Non-coding RNAs (ncRNAs) are critical regulators of gene expression in essentially all life forms. Long ncRNAs (lncRNAs) and microRNAs (miRNAs) are two important RNA classes possessing regulatory functions. Up to date, many primate-specific ncRNAs have been identified and investigated. Their expression specificity to primate lineage suggests primate-specific roles. It is thus critical to elucidate the biological significance of primate or even human-specific ncRNAs, and to develop potential ncRNA-based therapeutics. Here, we have summarized the studies regarding regulatory roles of some key primate-specific lncRNAs and miRNAs.

Page 187-195

6. Enhancer-derived RNA: A Primer

Feng Liu

Enhancer-derived RNAs (eRNAs) are a group of RNAs transcribed by RNA polymerase II from the domain of transcription enhancers, a major type of cis-regulatory elements in the genome. The correlation between eRNA production and enhancer activity has stimulated studies on the potential role of eRNAs in transcriptional regulation. Additionally, eRNA has also served as a marker for global identification of enhancers. Here I review the brief history and fascinating properties of eRNAs.

Page 196-200

7. Non-coding Transcripts from Enhancers: New Insights into Enhancer Activity and Gene Expression Regulation

Hongjun Chen, Guangshi Du, Xu Song, Ling Li

Long non-coding RNAs (lncRNAs) have gained widespread interest in the past decade owing to their enormous amount and surprising functions implicated in a variety of biological processes. Some lncRNAs exert function as enhancers, i.e., activating gene transcription by serving as the cis-regulatory molecules. Furthermore, recent studies have demonstrated that many enhancer elements can be transcribed and produce RNA molecules, which are termed as enhancer RNAs (eRNAs). The eRNAs are not merely the by-product of the enhancer transcription. In fact, many of them directly exert or regulate enhancer activity in gene activation through diverse mechanisms. Here, we provide an overview of enhancer activity, transcription of enhancer itself, characteristics of eRNAs, as well as their roles in regulating enhancer activity and gene expression.
经过十余年的探索,目前已经发现lncRNA在生长发育、细胞凋亡、肿瘤发生等众多生理病理过程中以多种形式发挥调控效应,其生物学功能也受到科研工作者的重视。lncRNA可通过与其他生物大分子的相互作用发挥功能,并通过顺式或反式作用的方式调节目的基因的表达。新近研究表明基因增强子也可以进行转录,其转录产物被称为增强子RNA(enhancer RNA,eRNA)。研究显示这些eRNA能够发挥类似于lncRNA的基因表达调控功能。本文以增进对eRNA的了解为目的,对增强子、增强子的转录、eRNA的特点以及eRNA的作用机制进行讨论,并探讨了eRNAs如何介导增强子的功能以及如何调节基因表达。

Page 201-207

8. Downregulation of miR-503 Promotes ESCC Cell Proliferation, Migration, and Invasion by Targeting Cyclin D1

Lanfang Jiang, Zitong Zhao, Leilei Zheng, Liyan Xue, Qimin Zhan, Yongmei Song

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers in China, but the underlying molecular mechanism of ESCC is still unclear. Involvement of microRNAs has been demonstrated in cancer initiation and progression. Despite the reported function of miR-503 in several human cancers, its detailed anti-oncogenic role and clinical significance in ESCC remain undefined. In this study, we examined miR-503 expression by qPCR and found the downregulation of miR-503 expression in ESCC tissue relative to adjacent normal tissues. Further investigation in the effect of miR-503 on ESCC cell proliferation, migration, and invasion showed that enhanced expression of miR-503 inhibited ESCC aggressive phenotype and overexpression of CCND1 reversed the effect of miR-503-mediated ESCC cell aggressive phenotype. Our study further identified CCND1 as the target gene of miR-503. Thus, miR-503 functions as a tumor suppressor and has an important role in ESCC by targeting CCND1.
食管癌是恶性程度最高的癌种之一,其死亡率占世界癌症相关死亡率的第六位。中国的食管癌患者数量居世界首位。根据病理学分类,可将食管癌分为两种亚型,即食管鳞状细胞癌(ESCC)和食管腺癌(EAC),而中国的食管癌患者绝大部分是食管鳞状细胞癌﹙﹥90%﹚。目前,食管鳞状细胞癌的临床治疗手段有限,中国食管癌患者的五年生存率低于20%。因此,进一步探究食管鳞癌的发病机理、筛选食管鳞癌诊断的分子标志物、寻找有效的药物靶点具有重要的临床意义。microRNAs与食管癌的发生、转移和预后密切相关,miR-503被报道在多种肿瘤中发挥抑癌基因的作用,但其在食管癌中的作用机制尚不明确。本文是关于miR-503在食管癌中作用机制的研究。我们研究发现miR-503在食管癌组织中的表达低于配对的癌旁组织;功能研究发现,miR-503可抑制食管癌细胞的增殖、侵袭和迁移并导致细胞周期G1/S期的阻滞。细胞周期蛋白CyclinD1与食管癌的发生发展密切相关。数据库预测、Western Blot、结合荧光素酶报告基因实验表明CCND1是miR-503的靶基因。过表达miR-503可以抑制CCND1 mRNA和蛋白水平的表达。回复实验结果表明CCND1可以部分回复miR-503对细胞恶性表型的抑制作用。qPCR结果显示,CCND1 mRNA在食管癌组织中的表达低于其在配对的癌旁正常组织中的表达,且与miR-503的表达呈负相关。以上结果说明miR-503通过靶向CCND1抑制食管癌细胞的恶性表型,miR-503在食管癌中发挥抑癌基因的作用。

Page 208-217

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