长链非编码RNA与肿瘤的关系及其临床价值

长链非编码RNA（long non-coding RNA,IncDNA）是指长度超过200个核苷酸、具有调控基因表达作用的非编码RNA。近年来研究表明,长链非编码RNA在肿瘤的发生、发展过程中发挥着促癌或抑癌作用,它们参与了细胞凋亡调控、肿瘤浸润与转移等过程;另外,它们还通过表观遗传调控的方式影响肿瘤细胞的生长。它们有希望成为新型肿瘤标志物和肿瘤治疗的靶点,在肿瘤诊断和治疗方面显示出良好的临床应用前号。     

Human long non-coding RNAs promote pluripotency and neuronal differentiation by association with chromatin modifiers and transcription factors

Long non-coding RNAs (lncRNAs) are a numerous class of newly discovered genes in the human genome, which have been proposed to be key regulators of biological processes, including stem cell pluripotency and neurogenesis. However, at present very little functional characterization of lncRNAs in human differentiation has been carried out. In the present study, we address this using human embryonic stem cells (hESCs) as a paradigm for pluripotency and neuronal differentiation. With a newly developed method, hESCs were robustly and efficiently differentiated into neurons, and we profiled the expression of thousands of lncRNAs using a custom-designed microarray. Some hESC-specific lncRNAs involved in pluripotency maintenance were identified, and shown to physically interact with SOX2, and PRC2 complex component, SUZ12. Using a similar approach, we identified lncRNAs required for neurogenesis. Knockdown studies indicated that loss of any of these lncRNAs blocked neurogenesis, and immunoprecipitation studies revealed physical association with REST and SUZ12. This study indicates that lncRNAs are important regulators of pluripotency and neurogenesis, and represents important evidence for an indispensable role of lncRNAs in human brain development.     

植物免疫反应中的小RNA

植物中的小RNA参与多种生物学过程,依据其起源及前体结构的不同主要分为两类:微小RNA(miRNAs)和小干扰RNA(siRNAs),它们的长度通常为21~24个核苷酸,在生物合成途径以及作用机制等方面存在差异。病原物侵染植物后常通过诱导或抑制小RNA分子来调节抗病相关基因的表达,进而调控植物与病原物的互作反应。文章就小RNA的生物合成、作用途径及其在植物与病原物互作中的调控机制等方面进行了综述。     

The DNA‐ and RNA‐binding protein FACTOR of DNA METHYLATION 1 requires XH domain‐mediated complex formation for its function in RNA‐directed DNA methylation

Studies have identified a sub‐group of SGS3‐LIKE proteins including FDM1–5 and IDN2 as key components of RNA‐directed DNA methylation pathway (RdDM). Although FDM1 and IDN2 bind RNAs with 5′ overhangs, their functions in the RdDM pathway remain to be examined. Here we show that FDM1 interacts with itself and with IDN2. Gel filtration suggests that FDM1 may exist as a homodimer in a heterotetramer complex in vivo. The XH domain of FDM1 mediates the FDM1–FDM1 and FDM1–IDN2 interactions. Deletion of the XH domain disrupts FDM1 complex formation and results in loss‐of‐function of FDM1. These results demonstrate that XH domain‐mediated complex formation of FDM1 is required for its function in RdDM. In addition, FDM1 binds unmethylated but not methylated DNAs through its coiled‐coil domain. RNAs with 5′ overhangs does not compete with DNA for binding by FDM1, indicating that FDM1 may bind DNA and RNA simultaneously. These results provide insight into how FDM1 functions in RdDM.     

Transgenerational maintenance of transgene body CG but not CHG and CHH methylation

In plants, RNA-directed DNA methylation (RdDM) can target both transgene promoters and coding regions/gene bodies. RdDM leads to methylation of cytosines in all sequence contexts: CG, CHG and CHH. Upon segregation of the RdDM trigger, at least CG methylation can be maintained at promoter regions in the progeny. So far, it is not clear whether coding region methylation can be also maintained. We showed that the body of Potato spindle tuber viroid (PSTVd) transgene constructs became densely de novo methylated at CG, CHG and CHH sites upon PSTVd infection. In this study, we demonstrate that in viroid-free progeny plants, asymmetric CHH and CHG methylation was completely lost. However, symmetric CG methylation was stably maintained for at least two generations. Importantly, the presence of transgene body methylation did not lead to an increase of dimethylation of histone H3 lysine 9 or a decrease of acetylation of H3. Our data supports the view that CG methylation can be maintained not only in promoters but also in the body of transgenes. They further suggest that maintenance of methylation may occur independently of tested chromatin modifications.     

高通量测序技术及其在表观遗传学上的应用

DNA测序技术是现代生命科学研究的重要工具之一,而高通量测序技术在全基因组的研究中发挥着越来越重要的作用。简要回溯DNA测序技术的产生与发展,着重从PCR扩增测序和单分子测序两个方面全面描述了高通量测序中众多代表性的技术及直接测序技术,并从DNA甲基化、组蛋白修饰、非编码RNA调控等方面阐述了高通量测序技术在表观遗传学上的运用。     

核仁小RNA 在肿瘤发生中的作用

核仁小RNA（small nucleolar RNA,snoRNA）是一类真核细胞核仁中的60～300个核苷酸长度的非编码RNA,主要参与rRNA和其它小RNA转录后的成熟加工过程. 它们与肿瘤的关系曾一度被人们所忽视,然而,近年来有关snoRNA新功能的研究证明,它们与肿瘤的发生、发展密切相关. snoRNA以多种方式参与肿瘤的发生：一些snoRNA（如：U50、SNORD12、SNORD12b、SNORD12c、SNORD44和h5sn2等）具有抑癌活性,而另一些snoRNA（如：SNORD33、SNORD66、SNORD76、SNORD112、SNORD113、SNORD114、SNORA42、U70C和ACA59B等）具有促癌活性. 另外,编码snoRNA基因的异常也被发现与肿瘤的发生有关. 因此,开展snoRNA与肿瘤关系的研究将有可能为肿瘤诊治提供新线索.     

Xanthophylls are preferentially taken up compared with beta-carotene by retinal cells via a SRBI-dependent mechanism

The purpose of this study was to investigate the mechanisms by which carotenoids [xanthophylls vs. beta-carotene(beta-C)] are taken up by retinal pigment epithelial (RPE) cells. The human RPE cell line, ARPE-19, was used. When ARPE-19 cells were fully differentiated (7-9 weeks), the xanthophylls lutein (LUT) and zeaxanthin (ZEA) were taken up by cells to an extent 2-fold higher than beta-C (P < 0.05). At 9 weeks, cellular uptakes were 1.6, 2.5, and 3.2%, respectively, for beta-C, LUT, and ZEA. Similar extents were observed when carotenoids were delivered in either Tween 40 or "chylomicrons" produced by Caco-2 cells. Differentiated ARPE-19 cells did not exhibit any detectable beta-C 15,15'-oxygenase activity or convert exogenous beta-C into vitamin A. When using specific antibodies against the lipid transporters cluster determinant 36 (CD36) and scavenger receptor class B type I (SR-BI), cellular uptake of beta-C and ZEA were significantly decreased (40-60%) with anti-SR-BI but not with anti-CD36. Small interfering RNA transfection for SR-BI led to marked knockdown of SR-BI protein expression (approximately 90%), which resulted in decreased beta-C and ZEA uptakes by 51% and 87%, respectively. Thus, the present data show that RPE cells preferentially take up xanthophylls versus the carotene by a process that appears to be entirely SR-BI-dependent for ZEA and partly so for beta-C. This mechanism may explain, in part, the preferential accumulation of xanthophylls in the macula of the retina.