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| 1 | FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis显示文摘 | Xu Zhao Ying Yang Bao-Fa Sun Yue Shi Xin Yang Wen Xiao Ya-Juan Hao Xiao-Li Ping Yu-Sheng Chen Wen-Jia Wang Kang-Xuan Jin Xing Wang Chun-Min Huang Yu Fu Xiao-Meng Ge Shu-Hui Song Hyun Seok Jeong Hiroyuki Yanagisawa Yamei Niu Gui-Fang Jia Wei Wu Wei-Min Tong Akimitsu Okamoto Chuan He Jannie M Rendtlew Danielsen Xiu-Jie Wang Yun-Gui Yang | 2014 | Cell Research2014，24，12： | 109 |
| 2 | Methylation Modifications in Eukaryotic Messenger RNA显示文摘RNA methylation modifications have been found for decades of years, which occur at different RNA types of numerous species, and their distribution is species-specific. However, people rarely know their biological functions. There are several identified methylation modifications in eukaryotic messenger RNA(mRNA), such as N7-methylguanosine(m7G) at the cap, N6-methyl-20-O-methyladenosine(m6Am), 20-O-methylation(Nm) within the cap and the internal positions, and internal N6-methyladenosine(m6A) and 5-methylcytosine(m5C). Among them, m7G cap was studied more clearly and found to have vital roles in several important mRNA processes like mRNA translation, stability and nuclear export. m6A as the most abundant modification in mRNA was found in the 1970s and has been proposed to function in mRNA splicing, translation, stability, transport and so on. m6A has been discovered as the first RNA reversible modification which is demethylated directly by human fat mass and obesity associated protein(FTO) and its homolog protein, alkylation repair homolog 5(ALKBH5). FTO has a special demethylation mechanism that demethylases m6A to A through two over-oxidative intermediate states: N6-hydroxymethyladenosine(hm6A) and N6-formyladenosine(f6A). The two newly discovered m6A demethylases, FTO and ALKBH5, significantly control energy homeostasis and spermatogenesis, respectively, indicating that the dynamic and reversible m6A,analogous to DNA and histone modifications, plays broad roles in biological kingdoms and brings us an emerging field 'RNA Epigenetics'. 5-methylcytosine(5mC) as an epigenetic mark in DNA has been studied widely, but m5C in mRNA is seldom explored. The bisulfide sequencing showed m5C is another abundant modification in mRNA, suggesting that it might be another RNA epigenetic mark.This review focuses on the main methylation modifications in mRNA to describe their formation, distribution, function and demethylation from the current knowledge and to provide future perspectives on functional studies. | Jun Liu Guifang Jia | 2014 | Journal of Genetics and Genomics2014，41，1： | 13 |
| 3 | RNA中6-甲基腺嘌呤的研究进展显示文摘RNA酶促共价修饰研究,尤其是m6A(6-甲基腺嘌呤),是RNA生物学研究的一个新兴领域。m6A是真核生物mRNA内部序列中最常见的一种转录后修饰形式,由包含3个独立组分的复合物mRNA:m6A甲基转移酶催化生成。最新研究发现肥胖相关蛋白FTO可以脱掉m6A上的甲基,表明该甲基化过程是可逆的。抑制或敲除m6A甲基转移酶会引起重要的表型变化,但是由于过去的检测方法受限,m6A确切的作用机制目前为止还不甚清楚。二代测序技术结合免疫沉淀方法为大规模检测m6A修饰并研究其作用机制提供了可能。文章主要综述了m6A的发现史、生成机制、组织和基因组分布、检测方法、生物学功能等及其最新研究进展,并通过比较3种IP-seq技术和数据分析的异同及优缺点,对m6A这种RNA表观修饰研究中尚未解决的问题进行了讨论。 | 李语丽 于军 宋述慧 | 2013 | 遗传2013，35，12： | 11 |
| 4 | DNA甲基化修饰对血管疾病稳态失衡的影响显示文摘自稳态平衡是机体生命活动的重要基础,在维持机体的正常生理功能中发挥重要作用。血管疾病中的稳态失衡受物理、化学、生物等内外环境改变及致病因素的影响,其中氧稳态、血流稳态、糖脂代谢稳态在内环境的影响中较为突出,由此引起的一系列表观遗传修饰将导致血管结构和功能的异常。表观遗传学中的DNA甲基化与血管疾病的发生发展密不可分。此外,5-羟甲基胞嘧啶(5-hydroxymethylcytosine,5hm C)及N6-甲基腺嘌呤(N6-methyladenine,m6A)作为新的修饰碱基,将为表观遗传学研究提供新的思路。文章主要对DNA甲基化修饰变异在血管疾病稳态失衡方面的研究进展进行了阐述。 | 陈晓颖 叶华丹 洪青晓 周安楠 汤琳琳 段世伟 | 2015 | 遗传2015，37，3： | 9 |
| 5 | 多柔比星体内外对心肌甲基化转移酶样3依赖的m^6A RNA甲基化修饰的影响显示文摘目的探讨多柔比星(DOX)诱导心肌损伤对甲基化转移酶样3(METTL3)的表达及其依赖的RNA N6甲基腺苷(m6)甲基化修饰水平的影响。方法 30只雄性SD大鼠隔天ip给予DOX 2 mg·kg^(-1),共7次;DOX 1μmol·L^(-1)单独或与N-乙酰-L-半胱氨酸(NAC)0.5 mmol·L^(-1)共同处理心肌细胞H9C2 24 h;HE染色观察大鼠心肌组织和心肌细胞形态变化,Masson染色检测大鼠心肌组织胶原纤维累积,免疫荧光、荧光定量PCR和Western蛋白印迹法分析大鼠心肌组织和心肌细胞H9C2中超氧化物歧化酶(SOD)、核因子E2相关因子2(Nrf2)、叉头转录因子O3(Foxo3a)、活化的胱天蛋白酶3、METTL3和METTL14的表达;采用m6A RNA甲基化定量检测试剂盒分析大鼠心肌组织和H9C2细胞总m6A RNA甲基化修饰水平。结果与正常对照组相比,DOX处理组大鼠心肌纤维排列紊乱,肌原纤维溶解严重且局部有炎症细胞浸润,心肌组织胶原纤维累积增加(P<0.05);心肌组织SOD,Foxo3a和Nrf2蛋白表达水平显著下降(P<0.05,P<0.01),METTL3在mRNA及蛋白表达水平均上调(P<0.01),活化的胱天蛋白酶3表达水平显著增加(P<0.01),但METL14表达水平无显著变化。心肌细胞实验结果显示,与细胞对照组相比,DOX诱导心肌细胞H9C2中METTL3 mRNA和蛋白表达水平均上调(P<0.01),并存在时间依赖性(r=0.8211,P<0.05),而METTL14仅在mRNA水平表达上调(P<0.05),蛋白水平变化不显著;与DOX处理组相比,NAC能部分抑制DOX诱导的SOD,Nfr2和Foxo3a下调(P<0.05,P<0.01),METTL3和活化的胱天蛋白酶3上调(P<0.05,P<0.01)。m6A RNA甲基化水平分析显示,DOX上调大鼠心肌组织总m6A RNA甲基化修饰水平(P<0.05),而NAC抑制DOX诱导的心肌细胞H9C2总m6A RNA甲基化修饰水平的上调(P<0.05)。结论 METTL3依赖的m6A RNA甲基化修饰可能影响心肌内氧化还原动态平衡而介导DOX心肌毒性作用。 | 孟祥雯 张雪洁 张波 李彩蓉 杨晓松 | 2018 | 中国药理学与毒理学杂志2018，32，12： | 4 |
| 6 | 补阳还五汤对Cav-1^(-/-)小鼠脑缺血后m^(6)A修饰和血管新生的影响显示文摘目的观察补阳还五汤对小窝蛋白1基因敲除(Cav-1^(-/-))小鼠脑缺血后N6-甲基腺苷(m^(6)A)修饰和血管新生的影响,探讨其可能的作用机制。方法将72只雄性野生型(WT)小鼠及Cav-1^(-/-)(KO)小鼠分别随机分为对照组、模型组和补阳还五汤组,采用大脑中动脉栓塞法制备脑缺血模型,补阳还五汤组予补阳还五汤(18.5 g/kg)灌胃,对照组和模型组予等体积蒸馏水灌胃,连续7 d。对小鼠进行神经行为学评分,试剂盒检测缺血侧皮质m^(6)A水平,HE染色观察缺血侧皮质病理变化,免疫荧光双标法检测缺血侧皮质血管新生情况,RT-qPCR检测缺血侧皮质甲基转移酶样3(METTL3)、甲基转移酶样14(METTL14)、肾母细胞瘤1相关蛋白(WTAP)、肥胖相关蛋白(FTO)及AlkB同系物5(ALKBH5)mRNA表达。结果与同基因型对照组比较,WT、KO模型组小鼠神经行为学评分及缺血侧皮质m^(6)A水平明显升高(P<0.01),缺血侧皮质出现病理形态损伤,血管性血友病因子(VWF)/Ki-67双标阳性细胞数明显增加(P<0.01),KO模型组小鼠缺血侧皮质WTAP mRNA表达明显升高(P<0.01),FTO和ALKBH5 mRNA表达明显下降(P<0.01);与同基因型模型组比较,WT、KO补阳还五汤组小鼠神经行为学评分及m^(6)A水平明显降低(P<0.01,P<0.05),缺血侧皮质病理形态损伤改善,VWF/Ki-67双标阳性细胞数目明显增加(P<0.05),KO补阳还五汤组小鼠缺血侧皮质WTAP mRNA表达明显降低(P<0.01),FTO和ALKBH5 mRNA表达明显升高(P<0.01,P<0.05)。WT模型组和WT补阳还五汤组各项指标优于KO组(P<0.01,P<0.05)。结论补阳还五汤可能通过Cav-1调控脑缺血小鼠m^(6)A修饰和血管新生,从而发挥保护脑缺血损伤作用。 | 徐雅倩 陈博威 田丰铭 刘英飞 易健 刘柏炎 | 2023 | 中国中医药信息杂志2023，30，7： | 4 |
| 7 | N^6-甲基腺苷参与砷致人体肺癌过程的生物信息学分析显示文摘目的探究N6-甲基腺苷(m6A)修饰参与人体砷暴露致肺癌的可能性,为m6A修饰在预防与控制砷致癌的作用及机制研究提供线索。方法从GEO数据库获取29份饮水砷暴露志愿者RNA表达谱数据与氧化应激的人源细胞样本表达谱数据,采用差异基因分析工具GEO2R筛选差异表达基因,并通过Clue GO和DAVID系统对差异表达基因进行功能注释;从癌症基因组图谱数据库获取59份正常志愿者基因表达谱数据与515份肺腺癌患者基因表达谱数据,采用Ualcan分析系统对肺腺癌患者m6A相关酶的表达水平以及预后进行分析。结果 RNA代谢过程与甲基转移酶活性分别是砷暴露差异表达基因的生物过程和分子功能;转录调节是砷暴露与其公认机制氧化应激共同的差异表达基因的生物过程;相比于健康志愿者,m6A甲基化酶(METTL3)与介导m6A修饰基因翻译的m6A结合蛋白(YTHDF1)在早期肺腺癌患者的表达明显升高(P <0. 05),同时,其他m6A甲基化酶(METTL14与WTAP)与去甲基化酶(FTO)明显下调(P <0. 05); m6A去甲基化酶FTO表达水平的高低与肺腺癌患者的预后密切相关(P <0. 05)。结论 m6A修饰可能参与人体砷暴露致肺癌的过程并受到m6A甲基化酶、去甲基化酶与m6A结合蛋白的影响。 | 赵田禾 孙东雷 李欣洋 张遵真 | 2019 | 现代预防医学2019，46，3： | 3 |
| 8 | 动态RNAm^6A甲基化修饰及其调控mRNA剪接机制(英文)显示文摘RNA 6-甲基腺嘌呤(m6A)动态修饰酶的研究及RNA m6A免疫沉淀及高通量测序技术(Me RIP-seq/m6A-seq)的快速发展,为揭示m6A在调控RNA加工、个体发育、分化、代谢及生殖等生物学功能提供了新契机.催化m6A修饰形成的甲基转移酶复合物至少包括了催化亚基METTL3和METTL14及调控亚基WTAP;加双氧酶家族蛋白FTO和ALKBH5作为m6A去甲基化酶催化m6A去甲基化;而m6A结合蛋白主要分布于细胞质的YTH结构域家族YTHDF1-3和细胞核的YTHDC1-2.扰动上述调控m6A动态的修饰酶活性可导致上千基因的表达变化,并影响m RNA稳定性及剪接加工等.本文综述了近期m6A甲基转移酶、去甲基化酶和结合蛋白的重要研究进展,并讨论了m6A调控RNA加工代谢尤其是pre-m RNA剪接的潜在作用机制. | 杨莹 孙宝发 肖文 杨鑫 孙慧颖 赵永良 杨运桂 | 2015 | Science Bulletin2015，60，1： | 3 |
| 9 | 表观遗传异常在肿瘤发生发展中的研究进展显示文摘肿瘤的发生、发展与表观遗传异常改变密切相关,其中5-胞嘧啶碱基甲基化(5-m C)和RNA的N6-甲基腺苷(m-6-A)是常见并极其重要的表观改变,具有高度保守性,几乎存在于所有生物体中,参与调控基因组稳定和表达,在分化发育和生殖过程中起有重要作用。研究发现DNA和RNA的高甲基化表观修饰在恶性肿瘤的发生、发展和侵袭转移中起重要作用。但这一过程可被一些去甲基化酶逆转,其中DNA去甲基化酶TET(ten-eleven translocation)酶家族和异柠檬酸脱氢酶(IDH)可催化5-m C成为5-羟甲基胞嘧啶,而RNA去甲基化酶肥胖风险基因和ALKBH5可逆转RNA的m-6-A修饰。本文综述DNA与RNA甲基化的生物学特征和机制及其在肿瘤中功能的研究进展。 | 陈青 代智 周俭 | 2015 | 上海医药2015，36，16： | 3 |
| 10 | The epigenetic landscape of exercise in cardiac health and disease显示文摘With the rising incidence of cardiovascular diseases,the concomitant mortality and morbidity impose huge burdens on quality of life and societal costs.It is generally accepted that physical inactivity is one of the major risk factors for cardiac disease and that exercise benefits the heart in both physiological and pathologic conditions.However,the molecular mechanisms governing the cardioprotective effects exerted by exercise remain incompletely understood.Most recently,an increasing number of studies indicate the involvement of epigenetic modifications in the promotion of cardiac health and prevention of cardiac disease.Exercise and other lifestyle factors extensively induce epigenetic modifications,including DNA/RNA methylation,histone post-translational modifications,and non-coding RNAs in multiple tissues,which may contribute to their positive effects in human health and diseases.In addition,several studies have shown that maternal or paternal exercise prevents age-associated or high-fat dietinduced metabolic dysfunction in the offspring,reinforcing the importance of epigenetics in mediating the beneficial effects of exercise.It has been shown that exercise can directly modify cardiac epigenetics to promote cardiac health and protect the heart against various pathological processes,or it can modify epigenetics in other tissues,which reduces the risk of cardiac disease and affords cardioprotection through exerkines.An in-depth understanding of the epigenetic landscape of cardioprotective response to exercise will provide new therapeutic targets for cardiac diseases.This review,therefore,aimed to acquaint the cardiac community with the rapidly advancing and evolving field of exercise and epigenetics. | Guiling Wu Xing Zhang Feng Gao | 2021 | Journal of Sport and Health Science2021，10，6： | 3 |
| 11 | 脂肪量和肥胖相关蛋白在人肾小管上皮细胞缺血再灌注损伤中的作用显示文摘目的探讨脂肪量和肥胖相关蛋白(FTO)在人近端肾小管上皮细胞(HK-2)缺血再灌注损伤(IRI)中的作用。方法以HK-2细胞作为研究对象,用抗霉素A、A23187、2-脱氧葡萄糖构建HK-2细胞IRI模型。将细胞分为对照组及缺血再灌注组(I/R组)。实时荧光PCR(qPCR)法及Western blot法分别检测2组细胞FTO、B细胞淋巴瘤/白血病2相关X基因(Bax)、B细胞淋巴瘤/白血病基因2(Bcl-2)、剪切型含半胱氨酸的天冬氨酸蛋白水解酶(cleaved Caspase-3)的mRNA及蛋白表达水平。流式细胞术检测细胞凋亡。比色法检测mRNA N^(6)-甲基腺苷(m^(6)A)甲基化水平。结果1.与对照组比较,I/R组细胞FTO mRNA(0.15±0.05比1.00±0.23)、Bcl-2 mRNA(0.14±0.07比1.02±0.25)相对表达量降低,Bax(3.10±0.35比1.00±0.13)、cleaved Caspase-3 mRNA(4.21±0.56比1.00±0.09)相对表达量增高,差异均有统计学意义(t=6.28、5.84、-9.83、-9.84,均P<0.01)。2.与对照组比较,I/R组FTO蛋白(0.69±0.14比1.37±0.02)、Bcl-2蛋白(0.50±0.12比1.25±0.21)降低,Bax蛋白(1.04±0.08比0.57±0.06)、cleaved Caspase-3蛋白(0.99±0.05比0.36±0.07)相关表达量增高,差异均有统计学意义(t=8.10、5.49、-8.22、-12.09,均P<0.05)。3.与对照组比较,I/R组HK-2细胞凋亡率[(61.70±1.01)%比(0.16±0.10)%]增高,差异有统计学意义(t=63.80,P<0.01)。4.与对照组比较,I/R组总mRNA m^(6)A水平在总RNA中的百分比[(3.13±0.21)%比(1.10±0.26)%]增高,差异有统计学意义(t=-10.61,P<0.01)。结论FTO介导的RNA m6A修饰可能通过调控HK-2细胞凋亡影响肾脏IRI。 | 熊冰瑶 康志娟 李志辉 | 2022 | 中华实用儿科临床杂志2022，37，8： | 2 |
| 12 | METTL3对皮肤鳞状细胞癌细胞的增殖和分化的影响研究显示文摘皮肤鳞状细胞癌来源于表皮干细胞的自我更新和分化的平衡失调。近来研究表明,甲基转移酶3(METTL3)介导的m6A修饰在多种癌症研究中成为前沿热点。然而, METTL3在皮肤鳞状细胞癌中的作用尚未报道。该研究目的在于了解METTL3在皮肤鳞状细胞癌发生中的作用。通过构建shRNA敲低皮肤鳞状细胞癌中METTL3,研究其对WTAP、METTL14以及m6A修饰水平的作用。此外,应用免疫组化、免疫印迹、qPCR以及裸鼠荷瘤实验,在体外和体内水平研究敲低METTL3对鳞状细胞癌增殖、分化和自我更新的影响。结果显示, METTL3在鳞状细胞癌细胞中表达上调。敲低METTL3能降低METTL14以及m6A修饰水平。敲低METTL3促进癌细胞的分化,并增加IKKα的表达;同时抑制癌细胞的增殖和自我更新,降低自我更新相关基因的表达。综上,该实验证明了METTL3在调节皮肤鳞状细胞癌细胞分化和自我更新中的关键作用。该研究也为皮肤鳞状细胞癌的治疗提供一个新的靶点。 | 周仁鹏 王琛 傅秀军 王丹茹 盛玲玲 梁奕敏 | 2019 | 中国细胞生物学学报2019，0，6： | 2 |
| 13 | mRNA修饰研究概况及展望显示文摘信使RNA的核苷酸修饰主要包括2'-O-甲基化、假尿嘧啶化、m6A、m5C、m7G、m1A、5hm C等。已有的研究表明,这些修饰在m RNA稳定性、加工、遗传信息传递以及细胞的应激反应中起到重要作用。由于技术的限制,过去我们对于m RNA修饰知之甚少。近年来,一系列新技术的产生为全面地考察m RNA核苷酸修饰状况,深入地研究它们的生物学功能提供了极大的便利,并且取得了一些重要的进展。就此方面的研究概况作简要概述。 | 孙文举 周克任 杨建华 周惠 屈良鹄 | 2016 | 生命科学2016，28，5： | 2 |
| 14 | m^(6) A修饰调控卵母细胞及早期胚胎发育的研究进展显示文摘N6-甲基腺苷(m^(6)A)修饰是广泛存在的一种表观修饰,在有性生殖卵子的发育与早期胚胎成熟中发挥重要作用。m^(6)A修饰呈现出动态变化,m^(6)A及相关甲基化酶、去甲基化酶和甲基化识别酶的表达参与各种生理活动,主要在调节转录、调控相关蛋白质翻译、影响mRNA稳定性及降解等方面发挥作用。围绕m^(6)A修饰在生殖领域的研究大多围绕配子减数分裂和胚胎早期阶段的发育。m^(6)A修饰关键基因影响某些相关信号通路,调控卵母细胞的减数分裂及受精后细胞增殖过程,异常m^(6)A修饰和相关酶表达则引起卵泡发育受阻、早期胚胎发育停滞。而m^(6)A修饰作为一种可逆的调控方式,或将为生殖医学领域疾病的研究提供新的科学思路。文章主要从卵母细胞及早期胚胎发育与m^(6)A、m^(6)A相关酶的缺乏对卵泡发育及早期胚胎发育的影响以及m^(6)A及相关酶与女性卵巢衰老的关系进行综述。 | 王领弟(综述) 杨洪艳(审校) | 2021 | 医学研究生学报2021，34，3： | 2 |
| 15 | 甲基转移酶3调控pri-miR-21甲基化修饰在糖尿病肾病肾脏纤维化中的作用显示文摘目的·探讨甲基转移酶3(methyltransferase like 3,METTL3)调控pri-miR-21的N^(6)-甲基腺苷(N^(6)-methyladenosine,m^(6)A)甲基化修饰在糖尿病肾病(diabetic nephropathy,DN)小鼠肾脏纤维化发病机制中的作用。方法·采用8周龄雄性db/db小鼠作为DN模型小鼠,db/m小鼠作为对照,同时按照是否经尾静脉注射S-腺苷高半胱氨酸水解酶抑制剂3-脱氮腺苷(3-deazaadenosine,DAA),共随机分为4组(5只/组),分别为db/m组、db/db组、db/m+DAA组和db/db+DAA组;8周龄开始注射DAA,注射1次/5 d,共注射8次。DAA干预结束后继续饲养小鼠至19周龄,收取各组小鼠血、尿、肾脏组织标本。检测血糖、血肌酐、尿白蛋白肌酐比(albumin-to-creatinine ratio,ACR),肾脏行苏木精-伊红(H-E)染色、Masson染色及天狼星红染色观察病理变化;试剂盒检测肾脏总RNA中m^(6)A的甲基化水平;Western blotting检测肾脏METTL3及纤维化相关蛋白表达;实时定量PCR检测肾脏总pri-miR-21和成熟miR-21;使用免疫磁珠富集肾脏组织中m^(6)A甲基化RNA,并通过PCR检测其中m^(6)A甲基化的pri-miR-21。结果·相较于db/m组,db/db组小鼠血糖,血肌酐,ACR,肾脏METTL3、m^(6)A甲基化修饰水平、纤维化相关蛋白、总pri-miR-21、m^(6)A甲基化pri-miR-21和成熟miR-21表达水平均显著增加(均P<0.05),小鼠肾脏系膜基质增多、肾小球基底膜增厚、胶原纤维累积显著增加。相较于db/db组,db/db+DAA组血糖,血肌酐,ACR,肾脏m^(6)A甲基化修饰水平、纤维化相关蛋白、m^(6)A甲基化pri-miR-21和成熟miR-21表达水平均显著下降(均P<0.05),总pri-miR-21表达水平显著升高(P=0.000),METTL3蛋白表达水平未见显著变化,小鼠肾脏损伤及纤维化程度显著减轻。结论·pri-miR-21的m^(6)A甲基化修饰促进miR-21成熟,进而促进DN小鼠肾脏纤维化的发生发展;抑制METTL3可通过调控pri-miR-21的m^(6)A甲基化修饰抑制DN小鼠肾脏纤维化。 | 吴佳晋 钟晨 李大伟 陈若洋 瞿俊文 张明 | 2023 | 上海交通大学学报(医学版)2023，43，1： | 1 |
| 16 | Amplification and function analysis of N6-adenine-specific DNA methyltransferase gene in Nilaparvata lugens显示文摘Methylation of the N6 position of adenine, termed N6-methyladenine, protects DNA from restriction endonucleases via the host-specific restriction-modification system. N6-methyladenine was discovered and has been well studied in bacteria. N6-adenine-specific DNA methyltransferase(N6AMT) is the main enzyme catalyzing the methylation of the adenine base and knowledge of this enzyme was mainly derived from work in prokaryotic models. However, large-scale gene discovery at the genome level in many model organisms indicated that the N6AMT gene also exists in eukaryotes, such as humans, mice, fruit flies and plants. Here, we cloned a N6AMT gene from Nilaparvata lugens(Nlu-N6AMT) and amplified its fulllength transcript. Then, we carried out a systematic investigation of N6AMT in 33 publically available insect genomes, indicating that all studied insects had N6AMT. Genomic structure analysis showed that insect N6AMT has short introns compared with the mammalian homologs. Domain and phylogenetic analysis indicated that insect N6AMT had a conserved N6-adenine Mlase domain that is specific to catalyze the adenine methylation. Nlu-N6AMT was highly expressed in the adult female. We knocked down Nlu-N6AMT by feeding ds RNA from the second instar nymph to adult female, inducing retard development of adult female. In all, we provide the first genome-wide analysis of N6AMT in insects and presented the experimental evidence that N6AMT might have important functions in reproductive development and ovary maturation. | ZHANG Jiao XING Yan-ru HOU Bo-feng YUAN Zhu-ting LI Yao JIE Wen-cai SUN Yang LI Fei | 2016 | Journal of Integrative Agriculture2016，15，3： | 1 |
| 17 | m6A-TSHub:Unveiling the Context-specific m^(6)A Methylation and m^(6)A-affecting Mutations in 23 Human Tissues显示文摘As the most pervasive epigenetic marker present on mRNAs and long non-coding RNAs(lncRNAs),N6-methyladenosine(m^(6)A)RNA methylation has been shown to participate in essential biological processes.Recent studies have revealed the distinct patterns of m^(6)A methylome across human tissues,and a major challenge remains in elucidating the tissue-specific presence and circuitry of m^(6)A methylation.We present here a comprehensive online platform,m^(6)A-TSHub,for unveiling the context-specific m^(6)A methylation and genetic mutations that potentially regulate m^(6)A epigenetic mark.m^(6)A-TSHub consists of four core components,including(1)m^(6)A-TSDB,a comprehensive database of 184,554 functionally annotated m^(6)A sites derived from 23 human tissues and 499,369 m^(6)A sites from 25 tumor conditions,respectively;(2)m^(6)A-TSFinder,a web server for high-accuracy prediction of m^(6)A methylation sites within a specific tissue from RNA sequences,which was constructed using multi-instance deep neural networks with gated attention;(3)m^(6)ATSVar,a web server for assessing the impact of genetic variants on tissue-specific m^(6)A RNA modifications;and(4)m^(6)A-CAVar,a database of 587,983 The Cancer Genome Atlas(TCGA)cancer mutations(derived from 27 cancer types)that were predicted to affect m^(6)A modifications in the primary tissue of cancers.The database should make a useful resource for studying the m^(6)A methylome and the genetic factors of epitranscriptome disturbance in a specific tissue(or cancer type).m^(6)A-TSHub is accessible at www.xjtlu.edu.cn/biologicalsciences/m^(6)ats. | Bowen Song Daiyun Huang Yuxin Zhang Zhen Wei Jionglong Su João Pedro de Magalhães Daniel J.Rigden Jia Meng Kunqi Chen | 2023 | Genomics, Proteomics & Bioinformatics2023，21，4： | 1 |
| 18 | N^(6)-methyladenosine and Its Implications in Viruses显示文摘N6-methyladenine(m^(6)A)is the most abundant RNA modification in mammalian messenger RNAs(mRNAs),which participates in and regulates many important biological activities,such as tissue development and stem cell differentiation.Due to an improved understanding of m^(6)A,researchers have discovered that the biological function of m^(6)A can be linked to many stages of mRNA metabolism and that m^(6)A can regulate a variety of complex biological processes.In addition to its location on mammalian mRNAs,m^(6)A has been identified on viral transcripts.m^(6)A also plays important roles in the life cycle of many viruses and in viral replication in host cells.In this review,we briefly introduce the detection methods of m^(6)A,the m^(6)A-related proteins,and the functions of m^(6)A.We also summarize the effects of m^(6)A-related proteins on viral replication and infection.We hope that this review provides researchers with some insights for elucidating the complex mechanisms of the epitranscriptome related to viruses,and provides information for further study of the mechanisms of other modified nucleobases acting on processes such as viral replication.We also anticipate that this review can stimulate collaborative research from different fields,such as chemistry,biology,and medicine,and promote the development of antiviral drugs and vaccines. | Yafen Wang Xiang Zhou | 2023 | Genomics, Proteomics & Bioinformatics2023，21，4： | 1 |
| 19 | Specific Regulation of m^(6)A by SRSF7 Promotes the Progression of Glioblastoma显示文摘Serine/arginine-rich splicing factor 7(SRSF7),a known splicing factor,has been revealed to play oncogenic roles in multiple cancers.However,the mechanisms underlying its oncogenic roles have not been well addressed.Here,based on N6-methyladenosine(m^(6)A)co-methylation network analysis across diverse cell lines,we find that the gene expression of SRSF7 is positively correlated with glioblastoma(GBM)cell-specific m^(6)A methylation.We then indicate that SRSF7 is a novel m^(6)A regulator,which specifically facilitates the m^(6)A methylation near its binding sites on the mRNAs involved in cell proliferation and migration,through recruiting the methyltransferase complex.Moreover,SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m^(6)A methyltransferase.The two m^(6)A sites on the mRNA for PDZ-binding kinase(PBK)are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2(IGF2BP2).Together,our discovery reveals a novel role of SRSF7 in regulating m^(6)A and validates the presence and functional importance of temporal-and spatial-specific regulation of m^(6)A mediated by RNA-binding proteins(RBPs). | Yixian Cun Sanqi An Haiqing Zheng Jing Lan Wenfang Chen Wanjun Luo Chengguo Yao Xincheng Li Xiang Huang Xiang Sun Zehong Wu Yameng Hu Ziwen Li Shuxia Zhang Geyan Wu Meisongzhu Yang Miaoling Tang Ruyuan Yu Xinyi Liao Guicheng Gao Wei Zhao Jinkai Wang Jun Li | 2023 | Genomics, Proteomics & Bioinformatics2023，21，4： | 1 |
| 20 | METTL16在鸡不同类型肌肉中的表达规律及其对肌肉功能的调控作用显示文摘旨在了解m6A甲基转移酶样蛋白16(methyltransferase-like protein 16,METTL16)在鸡不同类型肌肉组织中的表达情况及其在鸡骨骼肌功能中的调控作用。本研究利用qRT-PCR技术检测METTL16基因在120日龄广西麻鸡母鸡不同类型肌肉组织中的表达,同时利用siRNA干扰鸡原代成肌细胞中METTL16基因的表达,分析其对成肌细胞增殖、分化和肌纤维形成的影响。结果显示,METTL16基因在鸡的不同类型肌肉组织(胸大肌、胸小肌、缝匠肌、耻坐骨肌内侧肌、耻坐骨肌外侧肌、髂胫外侧肌、腓肠肌内侧肌和背阔肌)中广泛表达,其中,在白肌纤维为主的胸大肌、胸小肌和髂胫外侧肌中表达量相对更高;细胞增殖检测结果显示,干扰METTL16基因表达后,鸡成肌细胞的增殖活力受到了抑制;在成肌细胞分化后干扰METTL16基因表达,鸡成肌细胞RNA m6A甲基化水平呈下降趋势,细胞分化关键基因MyoD表达显著下降(P<0.05),fast-MyHC基因表达显著上升(P<0.001),slow-MyHC基因表达呈下降趋势。综上,METTL16基因在不同类型肌肉中的表达与其肌纤维类型组成相关,METTL16基因可能在鸡成肌细胞增殖和分化中发挥重要作用,并抑制快肌纤维的形成,提示METTL16可能在鸡肌肉功能调控中发挥重要作用。 | 庞立川 单艳菊 刘一帆 章明 甘达峰 屠云洁 姬改革 巨晓军 束婧婷 邹剑敏 | 2023 | 畜牧兽医学报2023，54，2： | 1 |
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