Membrane voltage is an important biophysical signal. Optical mapping of membrane voltage enables investigation of electrical signaling at high spatial resolutions and with high throughput. Here, we present a novel flu...
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Membrane voltage is an important biophysical signal. Optical mapping of membrane voltage enables investigation of electrical signaling at high spatial resolutions and with high throughput. Here, we present a novel fluorescent voltage indicator scaffold(FlareFRET) that builds upon site-specific modification of microbial rhodopsin with organic fluorophores. FlareFRET achieved 36% ΔF/F per100 mV voltage change with sub-millisecond response kinetics, thus representing one of the most sensitive and fastest orange-colored voltage indicators. This technique has enabled observation of long-range electrical coupling among mammalian cells that was mediated via gap-junctions. Combining the superior brightness and photostability of small molecules with genetic targeting of microbial rhodopsin proteins, the FlareFRET design strategy can be extended for developing novel fluorescent indicators.
N6-甲基腺嘌呤(N6-methyladenosine,m6A)是真核生物信使RNA(Messenger RNA,m RNA)上含量最多的化学修饰之一。类似于DNA和组蛋白化学修饰,m6A修饰也同样是动态可逆的,可在时间和空间上被甲基转移酶和去甲基酶调控。哺乳动物体内m6A甲基转移酶复合物中有一部分成分已被解析,主要有METTL3(Methyltransferase-like protein 3)、METTL14(Methyltransferase-like protein 14)和WTAP(Wilms tumor 1-associating protein)。m6A去甲基酶肥胖蛋白FTO(Fat mass and obesity associated protein)和ALKBH5(Alk B homolog 5)依赖α-酮戊二酸(α-Ketoglutaric acid,α-KG)和Fe(Ⅱ)对m6A进行氧化去甲基化反应。m6A在生物体内由m6A结合蛋白识别,并介导其行使功能。目前发现的m6A结合蛋白有YTH结构域蛋白YTHDF1(YTH domain-containing family protein 1)、YTHDF2(YTH domain-containing family protein 2)、YTHDC1(YTH domain-containing protein1)和核内HNRNPA2B1(Heterogeneous nuclear ribonucleoproteins A2B1)。本文综述了m6A的分布和相关蛋白介导的m6A功能研究,以期全面理解m6A这一RNA表观遗传新修饰在生命进程中的重要调控作用。
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