DNMT1 inhibition by pUG-fold quadruplex RNA.
DNMT1 inhibition by pUG-fold quadruplex RNA.
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DOI：
10.1261/rna.079479.122
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发表时间：
2023-03
期刊：
影响因子：
--
通讯作者：
Cech TR
中科院分区：
文献类型：
--
作者：
Jansson-Fritzberg LI;Sousa CI;Smallegan MJ;Song JJ;Gooding AR;Kasinath V;Rinn JL;Cech TR
DNA甲基化异常是癌症最早的标志之一。DNMT 1负责甲基化新复制的DNA，但DNMT 1的精确调节以确保忠实的DNA甲基化仍然知之甚少。最近出现了RNA和染色质相关蛋白之间的联系，一些研究表明DNMT 1可以由多种RNA调节。在这项研究中，我们证实了人DNMT 1确实与多种RNA相互作用，包括其自身的核mRNA。出乎意料的是，我们发现DNMT 1对形成pUG折叠（非经典G-四链体）的富含GU的RNA表现出强烈的特异性亲和力。我们发现，pUG折叠能力的RNA抑制DNMT 1活性抑制半甲基化的DNA的结合，我们还提供了证据与DNMT 1的多种RNA结合模式。总之，我们的数据表明，人类染色质相关蛋白结合到pUG折叠RNA，并受其调节。
Aberrant DNA methylation is one of the earliest hallmarks of cancer. DNMT1 is responsible for methylating newly replicated DNA, but the precise regulation of DNMT1 to ensure faithful DNA methylation remains poorly understood. A link between RNA and chromatin-associated proteins has recently emerged, and several studies have shown that DNMT1 can be regulated by a variety of RNAs. In this study, we have confirmed that human DNMT1 indeed interacts with multiple RNAs, including its own nuclear mRNA. Unexpectedly, we found that DNMT1 exhibits a strong and specific affinity for GU-rich RNAs that form a pUG-fold, a noncanonical G-quadruplex. We find that pUG-fold-capable RNAs inhibit DNMT1 activity by inhibiting binding of hemimethylated DNA, and we additionally provide evidence for multiple RNA binding modes with DNMT1. Together, our data indicate that a human chromatin-associated protein binds to and is regulated by pUG-fold RNA.
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影响因子：
30.8
作者：
Long, Yicheng;Hwang, Taeyoung;Gooding, Anne R.;Goodrich, Karen J.;Rinn, John L.;Cech, Thomas R.
通讯作者：
Cech, Thomas R.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
16.6
作者：
Kikuchi, Amika;Onoda, Hiroki;Yamaguchi, Kosuke;Kori, Satomi;Matsuzawa, Shun;Chiba, Yoshie;Tanimoto, Shota;Yoshimi, Sae;Sato, Hiroki;Yamagata, Atsushi;Shirouzu, Mikako;Adachi, Naruhiko;Sharif, Jafar;Koseki, Haruhiko;Nishiyama, Atsuya;Nakanishi, Makoto;Defossez, Pierre-Antoine;Arita, Kyohei
通讯作者：
Arita, Kyohei
影响因子：
3.7
作者：
Jeltsch, Albert
通讯作者：
Jeltsch, Albert
影响因子：
64.8
作者：
GRUENBAUM, Y;CEDAR, H;RAZIN, A
通讯作者：
RAZIN, A