Volume: 14, Issue: 2

Review Article

Long Non-coding RNAs in the Cytoplasm

Farooq Rashid, Abdullah Shah, Ge Shan

An enormous amount of long non-coding RNAs (lncRNAs) transcribed from eukaryotic genome are important regulators in different aspects of cellular events. Cytoplasm is the residence and the site of action for many lncRNAs. The cytoplasmic lncRNAs play indispensable roles with multiple molecular mechanisms in animal and human cells. In this review, we mainly talk about functions and the underlying mechanisms of lncRNAs in the cytoplasm. We highlight relatively well-studied examples of cytoplasmic lncRNAs for their roles in modulating mRNA stability, regulating mRNA translation, serving as competing endogenous RNAs, functioning as precursors of microRNAs, and mediating protein modifications. We also elaborate the perspectives of cytoplasmic lncRNA studies.

Page 73-80

Original Research

Genomic, Lipidomic and Metabolomic Analysis of Cyclooxygenase-null Cells: Eicosanoid Storm, Cross Talk, and Compensation by COX-1

Abul B.M.M.K. Islam, Mandar Dave, Sonia Amin, Roderick V. Jensen, Ashok R. Amin

The constitutively-expressed cyclooxygenase 1 (COX-1) and the inducible COX-2 are both involved in the conversion of arachidonic acid (AA) to prostaglandins (PGs). However, the functional roles of COX-1 at the cellular level remain unclear. We hypothesized that by comparing differential gene expression and eicosanoid metabolism in lung fibroblasts from wild-type (WT) mice and COX-2-/- or COX-1-/- mice may help address the functional roles of COX-1 in inflammation and other cellular functions. Compared to WT, the number of specifically-induced transcripts were altered descendingly as follows: COX-2-/- > COX-1-/- > WT + IL-1β. COX-1-/- or COX-2-/- cells shared about 50% of the induced transcripts with WT cells treated with IL-1β, respectively. An interactive “anti-inflammatory, proinflammatory, and redox-activated” signature in the protein–protein interactome map was observed in COX-2-/- cells. The augmented COX-1 mRNA (in COX-2-/- cells) was associated with the upregulation of mRNAs for glutathione S-transferase (GST), superoxide dismutase (SOD), NAD(P)H dehydrogenase quinone 1 (NQO1), aryl hydrocarbon receptor (AhR), peroxiredoxin, phospholipase, prostacyclin synthase, and prostaglandin E synthase, resulting in a significant increase in the levels of PGE2, PGD2, leukotriene B4 (LTB4), PGF1α, thromboxane B2 (TXB2), and PGF2α. The COX-1 plays a dominant role in shifting AA toward the LTB4 pathway and anti-inflammatory activities. Compared to WT, the upregulated COX-1 mRNA in COX-2-/- cells generated an “eicosanoid storm”. The genomic characteristics of COX-2-/- is similar to that of proinflammatory cells as observed in IL-1β induced WT cells. COX-1-/- and COX-2-/- cells exhibited compensation of various eicosanoids at the genomic and metabolic levels.

Page 81-93

Application Note

LVTree Viewer: An Interactive Display for the All-Species Living Tree Incorporating Automatic Comparison with Prokaryotic Systematics

Guanghong Zuo, Xiaoyang Zhi, Zhao Xu, Bailin Hao

We describe an interactive viewer for the All-Species Living Tree (LVTree). The viewer incorporates treeing and lineage information from the ARB-SILVA website. It allows collapsing the tree branches at different taxonomic ranks and expanding the collapsed branches as well, keeping the overall topology of the tree unchanged. It also enables the user to observe the consequence of trial lineage modifications by re-collapsing the tree. The system reports taxon statistics at all ranks automatically after each collapsing and re-collapsing. These features greatly facilitate the comparison of the 16S rRNA sequence phylogeny with prokaryotic taxonomy in a taxon by taxon manner. In view of the fact that the present prokaryotic systematics is largely based on 16S rRNA sequence analysis, the current viewer may help reveal discrepancies between phylogeny and taxonomy. As an application, we show that in the latest release of LVTree, based on 11,939 rRNA sequences, as few as 24 lineage modifications are enough to bring all but two phyla (Proteobacteria and Firmicutes) to monophyletic clusters.
自 Carl Woese 和同事们基于 16S rRNA 系统发生提出主要细菌门类描述以来，基于 16S rRNA 序列的亲缘关系已经被大多数生物学家接受。ARB-SILVA 的 ALL-Species Living Tree 项目，收集了当前绝大多细菌的 16S rRNA 构建了一棵覆盖几乎所有已知的原核生物物种的亲缘关系树，并不断更新。由于物种数过多，直接查看这棵亲缘关系树比较困难。LVTree Viewer 使用 HTML5 技术，将这棵进化树通过可伸缩与交互的方式显示在互联网上（http://tlife.fudan.edu.cn/lvtree），并自动的将其与分类关系进行比对。通过 LVTree Viewer，生物研究者可以方便的查看这棵具有一万多物种的亲缘关系树，并且与分类关系进行比对。通过使用 LVTree Viewer，我们研究了最近的一版的 LVTree，它根据 11939 条原核生物物种的 rRNA 序列而得到，通过综合考虑一些当前的研究结果，包括我们在 CVTree 方法的研究结果（http://tlife.fudan.edu.cn/cvtree3），我们发现只要对分类系统进行小的调整，就能够使得分类系统在门这一级别上与亲缘关系基本一致。我们相信，通过 LVTree Viewer 能够更加高效的比较亲缘关系与分类系统，从而探索更加合理的原核生物分类系统。

Page 94-102

Method

Similarity Estimation Between DNA Sequences Based on Local Pattern Histograms of Binary Images

Yusei Kobori, Satoshi Mizuta

Graphical representation of DNA sequences is one of the most popular techniques for alignment-free sequence comparison. Here, we propose a new method for the feature extraction of DNA sequences represented by binary images, by estimating the similarity between DNA sequences using the frequency histograms of local bitmap patterns of images. Our method shows linear time complexity for the length of DNA sequences, which is practical even when long sequences, such as whole genome sequences, are compared. We tested five distance measures for the estimation of sequence similarities, and found that the histogram intersection and Manhattan distance are the most appropriate ones for phylogenetic analyses.
DNA配列のグラフィカルな表現は、アライメントに依らない配列比較に関して 最も広く研究されている技術の一つである。本稿では、DNA配列間の類似性を 評価するために、DNA配列を2値画像で表し、その局所的なビットマップパター ンの出現頻度ヒストグラムを用いて配列の特徴を抽出するための新たな手法を 提案する。本手法はDNA配列の長さに関して線形の時間計算量を有し、全ゲノ ム配列のような大規模な配列に適用する場合においても実用的であることが示 される。ヒストグラム間の距離測度として代表的な5種の距離測度を用いてテ ストした結果、ヒストグラム交差法およびマンハッタン距離が、本手法を用い た系統解析に対して最も適切であるという結果が得られた。

Page 103-112

Letter

Up-regulation of Long Non-coding RNA TUG1 in Hibernating Thirteen-lined Ground Squirrels

Jacques J. Frigault, Daneck Lang-Ouellette, Pier Morin Jr.

Mammalian hibernation is associated with multiple physiological, biochemical, and molecular changes that allow animals to endure colder temperatures. We hypothesize that long non-coding RNAs (lncRNAs), a group of non-coding transcripts with diverse functions, are differentially expressed during hibernation. In this study, expression levels of lncRNAsH19 and TUG1 were assessed via qRT-PCR in liver, heart, and skeletal muscle tissues of the hibernating thirteen-lined ground squirrels (Ictidomys tridecemlineatus). TUG1 transcript levels were significantly elevated 1.94-fold in skeletal muscle of hibernating animals when compared with euthermic animals. Furthermore, transcript levels of HSF2 also increased 2.44-fold in the skeletal muscle in hibernating animals. HSF2 encodes a transcription factor that can be negatively regulated by TUG1 levels and that influences heat shock protein expression. Thus, these observations support the differential expression of the TUG1–HSF2 axis during hibernation. To our knowledge, this study provides the first evidence for differential expression of lncRNAs in torpid ground squirrels, adding lncRNAs as another group of transcripts modulated in this mammalian species during hibernation.
L’hibernation des mammifères est associée à de multiples changements physiologiques, biochimiques et moléculaires qui permettent aux animaux d’endurer les températures froides. Nous avons posé l’hypothèse que les longs ARNs non-codants (lncARNs), un groupe de transcrits non-codants avec des fonctions diverses, sont différentiellement exprimés durant l’hibernation. Dans cette étude, les niveaux d’expression des lncARNs H19 et TUG1 ont été évalués par qRT-PCR dans le foie, le cœur et les muscles squelettiques de l’écureuil hibernant Ictidomys tridecemlineatus. Les niveaux des transcrits de TUG1 ont notamment montré une élévation de 1.94-fois dans les muscles squelettiques des hibernants lorsque comparés aux niveaux obtenus chez les animaux contrôles. De plus, les niveaux des transcrits de HSF2 ont également montré une surexpression de 2.44-fois dans ces mêmes échantillons. HSF2 code pour un facteur de transcription qui peut être régulé négativement par les niveaux de TUG1 influençant ainsi l’expression de protéines de choc thermique. Ces observations supportent donc l’expression différentielle de l’axe TUG1-HSF2 durant l’hibernation. À notre connaissance, cette étude présente les premières évidences d’une expression différentielle de lncARNs dans des écureuils hibernants, ajoutant ainsi ceux-ci comme un groupe additionnel de transcrits modulés chez cet espèce lors de l’hibernation.

Page 113-118