植物MicroRNA功能的研究进展

MicroRNA(miRNA)是真核生物基因表达的一类负调控因子,植物miRNA主要在转录水平上通过介导靶基因的甲基化、在转录后水平介导靶mRNA的切割或降低靶mRNA的翻译来调节基因的表达,从而调控植物器官的形态建成、生长发育、激素分泌与信号转导以及植物对逆境胁迫因素的应答能力。该文主要综述了近年来植物miRNA在植物生长发育、激素调节与信号转导以及逆境胁迫应答中的重要作用,并针对miRNA的网络调控特征提出了今后miRNA功能研究的方向。     

植物microRNA与逆境响应研究进展

MieroRNA(miRNA)是一类在生物体内普遍存在的非编码、长度约16～29 nt的小分子RNA,由内源基因编码,于转录后水平通过介导靶mRNA降解或翻译抑制调控基因表达,是真核细胞基因表达的重要调控因子.随着生物信息学与研究技术的发展,越来越多的植物miRNA得到预测和验证.逆境胁迫下,植物体诱导或下调相关miRNA表达,参与植物逆境生理调节与适应.文章综述了植物miRNA生物合成、与靶基因的作用方式,生物功能以及逆境胁迫响应miRNA,概要介绍了目前常用的miRNA研究方法.     

动植物miRNA的生物合成、作用机理及其功能

microRNAs(miRNAs)是生物体内源长度约为20—23个核苷酸的非编码小RNA,通过与靶mRNA的互补配对而在转录后水平上对基因的表达进行负调控,导致mRNA的降解或翻译抑制。到目前为止,已报道有几千种miRNA存在于动物、植物、真菌等多细胞真核生物中,进化上高度保守。在植物和动物中,miRNA虽然都是通过与其靶基因的相互作用来调节基因表达,进而调控生物体的生长发育,但miRNA执行这种调控作用的机理却不尽相同。同时miRNA在动植物体内的形成过程也存在很多的不同之处。本文综述了动植物miRNA的生物合成、作用机理、生物功能等方面的研究进展。     

MicroRNA与动物发育

MicroRNA(miRNA)是一类约22nt大小的内源性非编码RNA,它们通过剪切靶基因的转录产物或者抑制转录产物的翻译从而起到转录后调控靶基因表达的作用。在动物体内,通过基因敲除等方法所进行的大量研究表明了miRNA参与了胚胎早期发育、脑及神经发育、心脏发育、肌肉及骨骼发育等动物发育的各个方面。miRNA是动物发生发育过程中重要的调控因子。主要介绍了近年来miRNA在动物生长发育过程中的研究进展。     

生长素响应因子与植物的生长发育

生长素响应因子(Auxin response factor, ARF)作为一类调控生长素响应基因表达的转录因子, 是生长素研究的重要内容。它可与生长素响应基因启动子区域内的生长素响应元件结合, 促进或抑制基因的表达。文章介绍了植物体内ARF家族的分子生物学近年来的研究进展, 同时也讨论了ARF转录因子的结构、ARF基因的表达调控、ARF在植物生长发育及信号转导中的作用以及ARF对靶基因的调控机制等内容。植物ARF成员都有一定的同源性, 大多含有4个结构域, 在多种组织和器官中都有表达, 其表达受到转录及转录后调控, 并且在介导生长素与其它激素之间相互作用方面扮演重要角色。     

miRNAs的表达调控机制

microRNAs(miRNAs)是一类在转录后基因调控中发挥功能的非编码小RNAs,在发育、生长和分化等过程中发挥重要作用.至今已经在动物、植物和微生物等不同生物体中鉴定出来数千种miRNAs. miRNAs可以通过降解mRNA或抑制蛋白翻译的方式调节特异基因表达.生物体内约30%的基因都受miRNAs的调节.miRNAs的表达与功能受到转录因子、表观遗传学、多核苷酸多态性及其RNA编辑等多种因素的调节.此外,特异miRNA基因敲除的成功为研究miRNAs功能提供了有力的实验模型.     

转录因子与疾病

在真核基因表达调控中起重要作用的转录因子与许多疾病的关系近来已得到证实,本综述了某些这类疾病的临床表现,受累的转录因子基因、转录因子结合的启动子及转录因子调节的靶基因在疾病发病过程中可能的作用,预期该领域的研究进展将为这些疾病的基因诊断或治疗提供依据。     

MnSOD基因表达调控的研究进展

MnSOD是生物体内重要的氧自由基清除剂, 具有抗氧化和抗肿瘤作用。MnSOD基因的表达调控是一个复杂的过程, 多种转录因子、细胞信号分子和细胞信号通路参与其中。MnSOD基因的表达调控包括转录调控、转录后调控和翻译调控3个方面。转录调控是MnSOD基因表达调控的第一个层次, 在MnSOD基因表达的过程中起重要作用。它主要是通过调节与MnSOD基因转录相关的转录因子活性来实现的, 例如特异蛋白-1 (SP-1)、激活蛋白-2(AP-2)、激活蛋白-1(AP-1)、核因子-卡巴B(NF-κB)等。药物和金属离子就是通过改变这些转录因子的活性来调控MnSOD基因表达的, 另外某些基因的突变和缺失也能改变这些转录因子的活性。转录后调控主要体现在改变mRNA的稳定性或mRNA的翻译上。翻译调控则是对MnSOD多肽的编辑、修饰并与相应的金属离子结合及定位的调控。近年来发现了一种线粒体MnSOD的锰转运因子, 它对MnSOD活性的调控起重要作用。文章综述了这一研究领域的一些进展, 着重讨论了MnSOD基因的转录调控和翻译调控, 并展望了MnSOD基因表达调控的研究方向。     

Comparisons of F Factors and R Factors: Existence of Independent Regulation Groups in F Factors

The similarity of sex pili mediated by F factors and R(fi(+)) factors and the ability of R(fi(+)) factors to control by repression the functioning of pilus genes encoded by the F factor suggested that F factors and R(fi(+)) factors are closely related. Further comparisons of the episomal properties of F factors and R(fi(+)) factors, however, indicated many differences. F factors contain information for a restriction system for phages phiII and T7. Cells containing R factors are sensitive to these phages. Furthermore, R(fi(+)) factors do not repress the F factor phiII restriction system in cells containing both an R(fi(+)) factor and an F factor. R factors and F factors are heteroimmune episomes. In addition, an R(fi(+)) factor in cells containing both an R factor and an F factor does not fully repress the expression of F-factor immunity to an incoming second F factor. R-factor and F-factor replication systems are not identical. Wild-type F-factor replication genes will complement the mutant F(ts114)lac(+) replication genes in cells containing two F factors. The F(ts114)lac(+) episome is retained when these cells are grown at 42 C; however, cells containing an R(fi(+)) factor and F(ts114)lac(+) lose the F(ts114)lac(+) when grown at 42 C, at the same rate as cells containing only the F(ts114)lac(+). The replication system of the R(fi(+)) factor will not complement the mutant F(ts114)lac(+) replication system.     

缺氧诱导因子

缺氧诱导因子 (ｈｙｐｏｘｉａ ｉｎｄｕｃｉｂｌｅｆａｃｔｏｒ,ＨＩＦ 1 )是在研究缺氧诱导的红细胞生成素(ｅｒｙｔｈｒｏｐｏｉｅｔｉｎ ,ＥＰＯ)基因表达时发现的一种ＤＮＡ结合蛋白。 1 988年 ,Ｇｏｌｄｂｅｒｇ等发现缺氧对细胞ＥＰＯｍＲＮＡ的表达有影响[1] 。1 991年 ,Ｓｅｍｅｎｚａ等发现 ,Ｈｅｐ3Ｂ细胞经低氧处理后 ,ＥＰＯ的ｍＲＮＡ量增加 ,且其核提取物具有促进ＥＰＯ基因转录的作用 ,蛋白合成抑制剂能阻断缺氧的诱导作用 ,故提出缺氧可以诱导细胞产生新的ＨＩＦ 1蛋白 ,该蛋白能够调节一系列基因的表达[2 ] 。 1 997年发…     

抗σ因子

Ｔ4噬菌体的ＡｓｉＡ可以抑制大肠杆菌的σ70 因子 ,因而称为抗σ70 因子 ,调节Ｔ4噬菌体早期基因的转录。细菌中的ＦｌｇＭ ,是抗σ2 8因子在细菌鞭毛形成过程中起调控作用。ＦｌｇＭ比较特殊 ,天然形式是未折叠的。枯草杆菌(Ｂａｃｉｌｌｕｓｓｕｂｔｉｌｉｓ)的ＳｐｏＩＩＡＢ可抑制芽孢形成过程的专一性σ因子σＦ 和σＧ。该菌中的另一个抗σ因子是ＲｓｂＷ可以抑制应急反应中基因转录所需的σＢ 因子。此外 ,在真细菌类中 ,发现一类新的具内膜接合特性的抗σ因子 ,调控着具有胞外功能蛋白的基因表达 ,因而被分作抗σ因子的细胞外因子 …     

Factors Influencing Aqueous Proinflammatory Cytokines and Growth Factors in Uveitic Glaucoma

Purpose

To analyze the effects of factors on aqueous humor proinflammatory cytokine and growth factor levels in patients with uveitic glaucoma (UG).

Methods

In this cross-sectional study, we enrolled 143 participants: 1) UG patients (n = 39); 2) primary open-angle glaucoma (POAG) patients (n = 36); and 3) cataract surgery patients, as a comparative group (n = 68). Aqueous humor samples were obtained at the start of surgery. Aqueous cytokine levels were determined using a multiplex immunoassay (xMAP and the Human Cytokine/Chemokine Panel I).

Results

In UG cases, mean interleukin (IL)-6, IL-8, monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-α, platelet-derived growth factor (PDGF)-AA, PDGF-AB/BB, and VEGF levels were 171.1, 214.5, 2791.7, 3.5, 23.9, 5.4, and 168.9 pg/mL, respectively, and were higher than those in cataract (non-glaucomatous) cases except PDGF. Levels of IL-6, MCP-1, and VEGF were higher in UG cases than in POAG cases. UG cases with a history of phacoemulsification displayed significantly higher levels of IL-6 (P = 0.0164), IL-8 (P = 0.0003), MCP-1 (P = 0.0465), and PDGF-AB/BB (P = 0.0062) compared to the phakic cases. The presence of cells in the anterior chamber was related to higher levels of IL-8 (P = 0.0002), TNF-α (P = 0.0037), and PDGF-AB/BB (P = 0.0009). The level of PDGF-AB/BB was higher in infectious uveitis than in non-infectious uveitis (P = 0.0211). The level of transforming growth factor (TGF)-β2 was negatively correlated with the levels of MCP-1 (adjusted R² = 0.28, t = -2.45, P = 0.031) and TNF-α (adjusted R² = 0.27, t = -2.43, P = 0.032).

Conclusion

A history of phacoemulsification, the presence of cells in the anterior chamber, and infectious uveitis were related to aqueous proinflammatory cytokine levels in patients with UG. TGF-β2 might be an anti-inflammatory factor in aqueous humor of UG patients.     

Hypoxia-Inducible Factors Activate CD133 Promoter through ETS Family Transcription Factors

CD133 is a cellular surface protein that has been reported to be a cancer stem cell marker, and thus it is considered to be a potential target for cancer treatment. However, the mechanism regulating CD133 expression is not yet understood. In this study, we analyzed the activity of five putative promoters (P1–P5) of CD133 in human embryonic kidney (HEK) 293 cells and colon cancer cell line WiDr, and found that the activity of promoters, particularly of P5, is elevated by overexpression of hypoxia-inducible factors (HIF-1α and HIF-2α). Deletion and mutation analysis identified one of the two E-twenty six (ETS) binding sites (EBSs) in the P5 region as being essential for its promoter activity induced by HIF-1α and HIF-2α. In addition, a chromatin imunoprecipitation assay demonstrated that HIF-1α and HIF-2α bind to the proximal P5 promoter at the EBSs. The immunoprecipitation assay showed that HIF-1α physically interacts with Elk1; however, HIF-2α did not bind to Elk1 or ETS1. Furthermore, knockdown of both HIF-1α and HIF-2α resulted in a reduction of CD133 expression in WiDr. Taken together, our results revealed that HIF-1α and HIF-2α activate CD133 promoter through ETS proteins.