长链非编码RNA的功能与疾病治疗的潜力

人类基因组转录本长度>200 nt（核苷酸）、不编码蛋白质的RNA分子为长链非编码RNA（long non-coding RNA,lncRNA)。lncRNA可在多个层面调节基因表达,其功能失调与包括肿瘤在内的很多人类疾病密切相关。本文概述lncRNA的种类、功能与疾病的关系,讨论基于lncRNA基因编辑、干细胞修饰及其与miRNA、蛋白质相互作用等的治疗潜能。     

哺乳动物中由精子RNA介导的跨代遗传的研究进展

随着表观遗传学的飞速发展,拉马克的获得性遗传理论又重新得到了学术界的关注．近年,哺乳动物获得性性状的跨代遗传现象也得到了较为深入的研究．在获得性性状的跨代遗传过程中,由环境压力导致的表观遗传信息经由生殖系在代际间传递．其中,在环境压力相关的表观遗传信息的建立及传递过程中,精子小非编码RNA(small non-coding RNA,sncRNAs)发挥关键作用,环境压力信息以sncRNAs的形式储存在成熟精子中,通过受精作用,精子sncRNAs参与胎儿原始生殖细胞基因组的表观遗传修饰,将表观遗传信息跨代传递,进而影响获得性性状相关的基因表达．本文主要综述了精子sncRNAs参与获得性性状跨代遗传的机制,为研究遗传性的代谢疾病、促进人类生殖健康及家畜良种繁育提供新思路．     

Faster ticking rate of the epigenetic clock is associated with faster pubertal development in girls

Epigenetic age is an indicator of biological aging, capturing the impact of environmental and behavioral influences across time on cellular function. Deviance between epigenetic age and chronological age (AgeAccel) is a predictor of health. Pubertal timing has similarly been associated with cancer risk and mortality rate among females. We examined the association between AgeAccel and pubertal timing and adolescent breast composition in the longitudinal Growth and Obesity Cohort Study. AgeAccel was estimated in whole blood using the Horvath method at breast Tanner 2 (B2) and 4 (B4). Total breast volume, absolute fibro-glandular volume (FGV), and %FGV were evaluated at B4 using dual X-ray absorptiometry. The impact of AgeAccel (mean: 0; SD: 3.78) across puberty on the time to breast development (thelarche), menarche, and pubertal tempo (thelarche to menarche) was estimated using accelerated failure time models; generalized estimating equations were used to evaluate associations with breast density. A five-year increase in average adolescent AgeAccel was associated with a significant decrease in time to menarche [hazard ratio (HR): 1.37; 95% confidence interval (CI): 1.04, 1.80] adjusting for birth weight, maternal pre-pregnancy body mass index, maternal height, maternal education, B2 height, fat percentage, and cell composition. AgeAccel displayed a stronger inverse association with pubertal tempo (HR: 1.48; 95% CI: 1.10, 1.99). A five-year increase in AgeAccel was associated with 5% greater %FGV, adjusting for B4 percent body fat, and maternal traits (95% CI: 1.01, 1.10). Our study provides unique insight into the influence of AgeAccel on pubertal development in girls, which may have implications for adult health.     

Long non‐coding RNAs in brain tumours: Focus on recent epigenetic findings in glioma

Glioma biology is a major focus in tumour research, primarily due to the aggressiveness and high mortality rate of its most aggressive form, glioblastoma. Progress in understanding the molecular mechanisms behind poor prognosis of glioblastoma, regardless of treatment approaches, has changed the classification of brain tumours after nearly 100 years of relying on anatomopathological criteria. Expanding knowledge in genetic, epigenetic and translational medicine is also beginning to contribute to further elucidating molecular dysregulation in glioma. Long non‐coding RNAs (lncRNAs) and their main representatives, large intergenic non‐coding RNAs (lincRNAs), have recently been under scrutiny in glioma research, revealing novel mechanisms of pathogenesis and reinforcing others. Among those confirmed was the reactivation of events significant for foetal brain development and neuronal commitment. Novel mechanisms of tumour suppression and activation of stem‐like behaviour in tumour cells have also been examined. Interestingly, these processes involve lncRNAs that are present both during normal brain development and in brain malignancies and their reactivation might be explained by epigenetic mechanisms, which we discuss in detail in the present review. In addition, the review discusses the lncRNAs‐induced changes, as well as epigenetic changes that are consequential for tumour formation, affecting, in turn, the expression of various types of lncRNAs.     

Evolution of heat‐shock protein expression underlying adaptive responses to environmental stress

Heat‐shock proteins (Hsps) and their cognates are primary mitigators of cell stress. With increasingly severe impacts of climate change and other human modifications of the biosphere, the ability of the heat‐shock system to affect evolutionary fitness in environments outside the laboratory and to evolve in response is topic of growing importance. Since the last major reviews, several advances have occurred. First, demonstrations of the heat‐shock response outside the laboratory now include many additional taxa and environments. Many of these demonstrations are only correlative, however. More importantly, technical advances in “omic” quantification of nucleic acids and proteins, genomewide association analysis, and manipulation of genes and their expression have enabled the field to move beyond correlation. Several consequent advances are already evident: The pathway from heat‐shock gene expression to stress tolerance in nature can be extremely complex, mediated through multiple biological processes and systems, and even multiple species. The underlying genes are more numerous, diverse and variable than previously appreciated, especially with respect to their regulatory variation and epigenetic changes. The impacts and limitations (e.g., due to trade‐offs) of natural selection on these genes have become more obvious and better established. At last, as evolutionary capacitors, Hsps may have distinctive impacts on the evolution of other genes and ecological consequences.     

Soy‐Derived Phytochemical Genistein Modifies Chromatome Topology to Restrict Cancer Cell Proliferation

Epidemiological data indicate that human cancer risk is significantly reduced by the consumption of soy‐based foods containing the “phytoestrogen” genistein, which can signal via host cell estrogen receptors. While additional chemoprotective effects of genistein induced by epigenetic factors have also been reported, the key molecules and mechanisms involved are poorly defined. We therefore investigated genistein effects on chromatin‐bound proteins in the estrogen receptor‐deficient cell line MDA‐MB‐231 which is insensitive to phytoestrogen signaling. After exposure to low‐dose genistein for >1 month, MDA‐MB‐231 cells exhibited stable epigenetic alterations that are analyzed via partial MNase digestion and TMT‐based quantitative proteomics. 3177 chromatin‐bound proteins are identified with high confidence, including 882 molecules that displayed altered binding topology after cell conditioning with genistein. Prolonged phytochemical exposure conferred heritable changes in the binding topology of key epigenetic regulators including ATRX, SUV39H1/H2, and HP1BP3 that are preserved in untreated progeny, resulting in sustained downregulation of proliferation genes and reduced cell growth. These data indicate that soy derivative genistein exerts complex estrogen receptor‐independent effects on the epigenome likely to influence tumorigenesis by restricting cell growth.     

MTV sings jubilation for telomere biology in Drosophila

Telomere protects the ends of linear chromosomes. Telomere dysfunction fuels genome instability that can lead to diseases such as cancer. For over 30 years, Drosophila has fascinated the field as the only major model organism that does not rely on the conserved telomerase enzyme for end protection. Instead of short DNA repeats at chromosome ends, Drosophila has domesticated retrotransposons. In addition, telomere protection can be entirely sequence-independent under normal laboratory conditions, again dissimilar to what has been established for telomerase-maintained systems. Despite these major differences, recent studies from us and others have revealed remarkable similarities between the 2 systems. In particular, with the identification of the MTV complex as an ssDNA binding complex essential for telomere integrity in Drosophila (Zhang et al. 2016 Plos Genetics), we have now established several universal principles that are intrinsic to chromosome extremities but independent of the underlying DNA sequences or the telomerase enzyme. Telomere studies in Drosophila will continue to yield fundamental insights that are instrumental to the understanding of the evolution of telomere and telomeric functions.     

Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming

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