LncRNA作为ceRNA调控肿瘤的发生发展

长链非编码RNA(lncRNA)是长度大于200 bp,不编码蛋白质的内源性RNA分子.近年来的研究表明,lncRNA可以作为一种竞争性内源RNA(competing endogenous RNA,ceRNA)吸附miRNA,参与靶基因的表达调控,从而在肿瘤的发生发展中发挥重要的作用.本文从lncRNA作为ceRNA发挥生物学功能这一角度,概述了相关lncRNA在肿瘤发生发展中的作用及机制.揭秘lncRNA与miRNA在肿瘤发生中的相互作用,将为肿瘤的诊断和治疗提供新思路.     

Differential Regulation of beta-1,3-Glucanase Messenger RNAs in Response to Pathogen Infection

The acidic, extracellular, glucan endo-1,3-β-glucosidases (EC 3.2.1.39; β-1,3-glucanases), pathogenesis-related proteins-2, -N, and -O (i.e. PR-2, PR-N, and PR-O) were purified from Nicotiana tabacum (tobacco) and their partial amino acid sequences determined. Based on these data, complementary DNA (cDNA) clones encoding the proteins were isolated. Additional cDNAs were isolated that encoded proteins approximately 90% identical with PR-2, PR-N, and PR-O. Although the proteins encoded by these cDNAs have not been identified, their deduced amino acid sequences have slightly basic or neutral calculated isoelectric points, as well as carboxy-terminal extensions. These physical characteristics are shared by the vacuolar form of β-1,3-glucanase and other vacuolar localized analogs of PR proteins, suggesting that the unidentified proteins may be similarly localized. A preliminary evolutionary model that separates the β-1,3-glucanase gene family from tobacco into at least five distinct subfamilies is proposed. The expression of β-1,3-glucanase messenger RNAs (mRNAs) in response to infection by tobacco mosaic virus was examined. Messages for the acidic glucanases were induced similarly to the mRNAs for other PR proteins. However, the basic glucanase showed a different response, suggesting that different isoforms are differentially regulated by tobacco mosaic virus infection at the mRNA level.     

Non-monotonic Response to Monotonic Stimulus: Regulation of Glyoxylate Shunt Gene-Expression Dynamics in Mycobacterium tuberculosis

Understanding how dynamical responses of biological networks are constrained by underlying network topology is one of the fundamental goals of systems biology. Here we employ monotone systems theory to formulate a theorem stating necessary conditions for non-monotonic time-response of a biochemical network to a monotonic stimulus. We apply this theorem to analyze the non-monotonic dynamics of the σ^B-regulated glyoxylate shunt gene expression in Mycobacterium tuberculosis cells exposed to hypoxia. We first demonstrate that the known network structure is inconsistent with observed dynamics. To resolve this inconsistency we employ the formulated theorem, modeling simulations and optimization along with follow-up dynamic experimental measurements. We show a requirement for post-translational modulation of σ^B activity in order to reconcile the network dynamics with its topology. The results of this analysis make testable experimental predictions and demonstrate wider applicability of the developed methodology to a wide class of biological systems.     

Frequency Response of a Protein to Local Conformational Perturbations

Signals created by local perturbations are known to propagate long distances through proteins via backbone connectivity and nonbonded interactions. In the current study, signal propagation from the flexible ligand binding loop to the rest of Protein Tyrosine Phosphatase 1B (PTP1B) was investigated using frequency response techniques. Using restrained Targeted Molecular Dynamics (TMD) potential on WPD and R loops, PTP1B was driven between its crystal structure conformations at different frequencies. Propagation of the local perturbation signal was manifested via peaks at the fundamental frequency and upper harmonics of 1/f distributed spectral density of atomic variables, such as C_α atoms, dihedral angles, or polar interaction distances. Frequency of perturbation was adjusted high enough (simulation length >∼10×period of a perturbation cycle) not to be clouded by random diffusional fluctuations, and low enough (<∼0.8 ns⁻¹) not to attenuate the propagating signal and enhance the contribution of the side-chains to the dissipation of the signals. Employing Discrete Fourier Transform (DFT) to TMD simulation trajectories of 16 cycles of conformational transitions at periods of 1.2 to 5 ns yielded C_α displacements consistent with those obtained from crystal structures. Identification of the perturbed atomic variables by statistical t-tests on log-log scale spectral densities revealed the extent of signal propagation in PTP1B, while phase angles of the filtered trajectories at the fundamental frequency were used to cluster collectively fluctuating elements. Hydrophobic interactions were found to have a higher contribution to signal transduction between side-chains compared to the role of polar interactions. Most of in-phase fluctuating residues on the signaling pathway were found to have high identity among PTP domains, and located over a wide region of PTP1B including the allosteric site. Due to its simplicity and efficiency, the suggested technique may find wide applications in identification of signaling pathways of different proteins.     

Cellular Dynamics of Small RNAs

ABSTRACT

This review highlights the unexpectedly complicated nuclear egress and nuclear import of small RNAs. Although nucleus/cytoplasm trafficking was thought to be restricted to snRNAs of many, but not all, eukaryotes, recent data indicate that such traffic may be more common than previously appreciated. First, in conflict with numerous previous reports, new information indicates that Saccharomyces cerevisiae snRNAs may cycle between the nucleus and the cytoplasm. Second, recent studies also provide evidence that other small RNAs that function exclusively in the nucleus—the budding yeast telomerase RNA and possibly small nucleolar RNAs—may exit to the cytoplasm, only to return to the nucleus. Third, nucleus/cytoplasm cycling of RNAs also occurs for RNAs that function solely in the cytoplasm, as it has been discovered that cytoplasmic tRNAs of budding yeast travel “retrograde” to the nucleus and, perhaps, back again to the cytoplasm to function in protein synthesis. Fourth, there is at least one example in ciliates of small double-stranded RNAs traveling multiple cycles between the cytoplasm and distinct nuclei to direct genome structure. This report discusses data that support or argue against nucleus/cytoplasm bidirectional movement for each category of small RNA and the possible roles that such movement may serve.     

植物长链非编码RNA调控发育与胁迫应答的研究进展

长链非编码RNAs（long non-coding RNAs,lncRNAs）是一类长度大于200个核苷酸、缺乏明显开放阅读框、很少或者不具有蛋白编码潜能的内源性RNA。鉴于lncRNAs低表达和低保守性的特点,早期阶段认为其是转录副产物,在生物体内不发挥生物学功能。随着对非编码RNA的深入研究,lncRNAs被认为是一种调控其他类型RNA的重要基因组分,参与发育和胁迫应答生物学过程。本文主要阐述lncRNAs的来源及分类、作用机制、lncRNAs在植物发育和胁迫应答方面的生物学功能,为lncRNAs在作物生产育种中的应用研究提供参考。     

基于脉冲扰动作用下的一个捕食者-食饵模型的动力学性质

基于害虫的生物控制和化学控制策略,考虑到化学杀虫剂对天敌的影响,利用脉冲微分方程建立了在不同的固定时刻分别喷洒杀虫剂和释放天敌的具有依氏(Ivlev)功能性反应的捕食者-食饵脉冲动力系统．证明了当脉冲周期小于某个临界值时,系统存在一个渐近稳定的害虫根除周期解,否则系统是持续生存的．通过分析表明如果采取有效的化学控制策略,那么这种综害虫合控制策略更有效．     

竞争性内源RNA:一种全新的基因表达调控模式

竞争性内源RNA(ceRNA)假说是一种全新的基因表达调控模式:mRNA、假基因转录物和长链非编码RNA等转录物通过microRNA应答元件竞争结合相同的microRNA来调控各自的表达水平,从而影响细胞的功能.迄今为止,多家实验室已从生物信息学、细胞生物学和动物实验等层面验证了该假说.本文追溯了ceRNA假说提出的历程,讨论了ceRNA调控网络的影响因素,并提出了一些有待进一步完善的内容.ceRNA假说大大拓展了人类基因组中功能遗传信息的范畴,也为解析一些人类疾病发生的机制提供了新线索.     

番茄响应生物胁迫相关miRNA的研究进展

mi RNA(micro RNA)是一类长约22 nt的非编码小RNA分子,参与植物生长发育和胁迫响应等过程。近年来,通过生物学实验和生物信息学预测两种方法,陆续发现了一些响应病毒、真菌和共生真菌胁迫的番茄mi RNA。这些mi RNA的研究以及ami RNA(artificial mi RNA)技术的应用,将为番茄乃至其他植物病害的防治提供新的契机。