SFPQ Is an FTO-Binding Protein that Facilitates the Demethylation Substrate Preference.,Cell Chemical Biology

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SFPQ Is an FTO-Binding Protein that Facilitates the Demethylation Substrate Preference.
Cell Chemical Biology ( IF 6.6 ) Pub Date : 2020-01-22 , DOI: 10.1016/j.chembiol.2020.01.002
Haiping Song ₁ , Ye Wang ₁ , Ruixiang Wang ₂ , Xiao Zhang ₁ , Yaping Liu ₁ , Guifang Jia ₁ , Peng R Chen ₃

Affiliation

The fat mass and obesity-associated protein (FTO) is the first identified demethylase of the internal RNA modification N6-methyladenosine (m6A), which also exhibits demethylation activity toward N6,2'-O-dimethyladenosine (m6Am) and N1-methyladenosine (m1A). Demethylation of m6A at specific sites on target transcripts is a key enzymatic function of FTO that modulates diverse physiological and/or pathological processes. However, how FTO selects target RNA and whether additional interaction proteins facilitate this process remain elusive. Herein, via the genetically encoded and site-specific photocrosslinking strategy, we identified the major RNA-binding protein SFPQ as a direct interaction partner of FTO. Our study showed that FTO and SFPQ were located in close proximity throughout the transcriptome and that overexpression of SFPQ led to the demethylation of adjacent m6As, likely through recruiting FTO to these specific RNA sites. These results uncovered a new layer of regulation mechanism that may assist FTO to gain substrate specificity.

中文翻译：

SFPQ是一种FTO结合蛋白，有助于去除甲基化底物。

脂肪和肥胖相关蛋白（FTO）是内部RNA修饰N6-甲基腺苷（m6A）的第一个鉴定出的脱甲基酶，它对N6,2'-O-二甲基腺苷（m6Am）和N1-甲基腺苷（ m1A）。目标转录本上特定位点的m6A脱甲基化是FTO的关键酶促功能，可调节多种生理和/或病理过程。但是，FTO如何选择靶RNA以及其他相互作用蛋白是否有助于该过程仍然遥遥无期。在这里，通过遗传编码和位点特异性的光交联策略，我们确定了主要的RNA结合蛋白SFPQ是FTO的直接相互作用伙伴。我们的研究表明FTO和SFPQ在整个转录组中都非常靠近，并且SFPQ的过表达导致相邻m6A的去甲基化，可能是通过将FTO募集到这些特定的RNA位点来实现的。这些结果揭示了新的调控机制层，可以帮助FTO获得底物特异性。

更新日期：2020-01-24

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