Glucocorticoid receptor and protein/RNA synthesis-dependent mechanisms underlie the control of synaptic plasticity by stress

Learning and memory are exquisitely sensitive to behavioral stress, but the underlying mechanisms are still poorly understood. Because activity-dependent persistent changes in synaptic strength are believed to mediate memory processes in brain areas such as the hippocampus we have examined the means by which stress affects synaptic plasticity in the CA1 region of the hippocampus of anesthetized rats, Inescapable behavioral stress (placement on an elevated platform for 30 min) switched the direction of plasticity, favoring low frequency stimulation-induced decreases in synaptic transmission (long-term depression, LTD), and opposing the induction of long-term potentiation by high frequency stimulation, We have discovered that glucocorticoid receptor activation mediates these effects of stress on LTD and longterm potentiation in a protein synthesis-dependent manner because they were prevented by the glucocorticoid receptor antagonist RU 38486 and the protein synthesis inhibitor emetine. Consistent with this, the ability of exogenously applied corticosterone in non-stressed rats to mimic the effects of stress on synaptic plasticity was also blocked by these agents, The enablement of low frequency stimulation-induced LTD by both stress and exogenous corticosterone was also blocked by the transcription inhibitor actinomycin D, Thus, naturally occurring synaptic plasticity is liable to be reversed in stressful situations via glucocorticoid receptor activation and mechanisms dependent on the synthesis of new protein and RNA, This indicates that the modulation of hippocampus-mediated learning by acute inescapable stress requires glucocorticoid receptor-dependent initiation of transcription and translation.

RNA 的历史与未来

核酶的发现使得人们有理由相信生命起源于RNA ,通过试管演化实验获得的各种各样的催化性RNA 更使人们 对地球历史早期的RNA 世界有了越来越多的了解。同时,随着RNA 结构和功能上非凡的多样性的日益被揭示,RNA 在未来的临床应用研究中所具有的巨大潜力也正逐渐显现出来。

稳定的RNA 发夹结构在人类88 个mRNA 编码区中的分布

　以UNCG, GNRA , CUU G (N = A , U , C 或G; R = G或A) 为端环能够形成稳定的、保 守的发夹结构. 它们具有特殊的结构特征, 并在体内发挥着重要的生物学功能. 这些稳定的发夹 广泛分布于体内rRNA , 催化RNA 和非编码mRNA 中. 但对人类88 个编码区mRNA 二级结构的 研究当中, 却没有发现C(UUCG) G发夹. 而且, 与rRNA 不同, 这些编码区mRNA 四环序列的 分布没有明显的偏好性.

RNA A_6膨胀环的动力学特征

通过对RNA A6膨胀环在水溶液中的动力学模拟发现,在A6膨胀环中,环区构象主要以非堆积构象为主,环区具有较大的构象柔性,膨胀环区链的构象波动对已形成的RNA分子弯折的影响不大,弯折角只是在小范围内变动,提示作为全局结构,带大尺寸膨胀环的RNA分子仍然具有一定的刚性,柔性主要表现在膨胀环区域.

Additional angles to calculate the deformation of RNA helices induced by bulge loops

Bulges are common features of folded RNA structures. The RNA axial kinking caused by bulges has been confirmed by many experiments. Usually, a kinking angle zeta and a bending angle theta are used to describe the kinking and twisting of RNA molecules containing bulges. Here, we present two additional angles (twist angle zeta(1), twist angle zeta(2)) to describe the deformation of RNA helices induced by bulge loops because only two angles (a kinking angle zeta and a bending angle theta) are not enough to define the deformation of RNA induced by bulges. (C) 2002 Elsevier Science B.V. All rights reserved.

Dynamics of RNA with A6 bulge loop

In order to understand the behavior of RNAs with large bulges In solution, molecular dynamics was performed on the RNA molecule in water with A6 bulge. The result of simulation showed that nonstacked conformation Is the main conformation in large bulges, and the backbone of large bulge is of great conformational flexibility, but bulges-induced bends are relatively rigid. The fluctuation in bulge has little influence on the bend angle of RNAs.

Stable RNA hairpins in 88 coding regions of human mRNA

RNA hairpins containing UNCG, GNRA, CUUG (N = A, U, C or G, R = G or A) loops are unusually thermodynamic stable and conserved structures. The structural features of these hairpin loops are very special, and they play very important roles in vivo. They are prevalent in rRNA, catalytic RNA and non-coding mRNA. However, the 5' C(UUCG)G 3' hairpin is not found in the folding structure of 88 human mRNA coding regions. It is also different from rRNA in that there is no preference for certain sequences among tetraloops in these 88 mRNA folding structures.

Statistical correlation between protein secondary structure and messenger RNA stem-loop structure

Anew integrated sequence-structure database, called IADE (Integrated ASTRAL-DSSP-EMBL), incorporating matching mRNA sequence, amino acid sequence, and protein secondary structural data, is constructed. It includes 648 protein domains. Based on the IADE database, we studied the relation between RNA stem-loop frequencies and protein secondary structure. It was found that the alpha-helices and beta-strands on proteins tend to be preferably "coded" by mRNA stem region, while the coils on proteins tend to be preferably "coded" by mRNA loop region. These tendencies are more obvious if we observe the structural words (SWs). An SW is defined by a four-amino-acid-fragment that shows the pronounced secondary structural (alpha-helix or beta-strand) propensity. It is demonstrated that the deduced correlation between protein and mRNA structure can hardly be explained as the stochastic fluctuation effect. (C) 2003 Wiley Periodicals, Inc.

Cardioviral RNA structure logo analysis: entropy, correlations, and prediction

In recent years, there has been an increased number of sequenced RNAs leading to the development of new RNA databases. Thus, predicting RNA structure from multiple alignments is an important issue to understand its function. Since RNA secondary structures are often conserved in evolution, developing methods to identify covariate sites in an alignment can be essential for discovering structural elements. Structure Logo is a technique established on the basis of entropy and mutual information measured to analyze RNA sequences from an alignment. We proposed an efficient Structure Logo approach to analyze conservations and correlations in a set of Cardioviral RNA sequences. The entropy and mutual information content were measured to examine the conservations and correlations, respectively. The conserved secondary structure motifs were predicted on the basis of the conservation and correlation analyses. Our predictive motifs were similar to the ones observed in the viral RNA structure database, and the correlations between bases also corresponded to the secondary structure in the database.

RNA干扰在抗病毒研究中的应用

国家自然科学基金海外杰出青年基金(30428024)资助

双链RNA病毒诱导的牙鲆胚胎细胞差减cDNA文库的构建

以紫外线灭活的dsRNA病毒草鱼出血病病毒(GCHV)诱导和模拟诱导的牙鲆胚胎细胞为材料,利用抑制性差减杂交(SSH)技术,成功构建了双链RNA病毒诱导的牙鲆胚胎细胞(FEC)差减cDNA文库。以管家基因αtub lin作为差减指标,经检测,该文库差减效率达210倍,表明经病毒诱导后某些差异表达基因也得到了相应倍数的富集。将获得的cDNA片段连接到pGEM T载体,PCR检测显示差减片段在250bp~2 000bp之间。该差减cDNA文库的构建为从分子水平研究牙鲆培养细胞对dsRNA病毒的免疫反应、以及进