小柯机器人

日本东京大学Suzuki, Tsutomu研究组发现可逆的 RNA 磷酸化可稳定 tRNA 以提高细胞耐热性。相关论文于2022年4月27日发表于国际顶尖学术期刊《自然》杂志上。

他们在来自嗜热古生菌的 tRNA 的第 47 位鉴定了 2'-磷酸尿苷（简称Up）。Up47 赋予 tRNA 热稳定性和核酸酶抗性。原生古菌 tRNA 的原子结构显示出由 Up47 稳定的独特亚稳态核心结构。Up47 的 2'-磷酸从 tRNA 核心突出并防止热变性过程中的骨架旋转。此外，他们鉴定了 arkI 基因，该基因编码一种负责 Up47 形成的古生菌 RNA 激酶。结构研究表明，ArkI 具有一个非经典激酶基序，周围环绕着一个用于 tRNA 结合的带正电荷的补丁。一种 arkI 敲除菌株在高温下生长缓慢，当第二种 tRNA 修饰酶耗尽时表现出合成生长缺陷。他们还鉴定了 KptA 的古细菌同系物作为在体外和体内有效地使 Up47 去磷酸化的橡皮擦。

总之，他们的研究结果表明，Up47 是一种由 ArkI 和 KptA 介导的可逆 RNA 修饰，可在极端环境条件下微调 tRNA 的结构刚性。

研究人员表示，转录后修饰在 tRNA 稳定性和功能中具有关键作用。在嗜热菌中，tRNA 被大量修饰以在极端生长温度下保持其热稳定性。

附：英文原文

Title: Reversible RNA phosphorylation stabilizes tRNA for cellular thermotolerance

Author: Ohira, Takayuki, Minowa, Keiichi, Sugiyama, Kei, Yamashita, Seisuke, Sakaguchi, Yuriko, Miyauchi, Kenjyo, Noguchi, Ryo, Kaneko, Akira, Orita, Izumi, Fukui, Toshiaki, Tomita, Kozo, Suzuki, Tsutomu

Issue&Volume: 2022-04-27

Abstract: Post-transcriptional modifications have critical roles in tRNA stability and function1,2,3,4. In thermophiles, tRNAs are heavily modified to maintain their thermal stability under extreme growth temperatures5,6. Here we identified 2′-phosphouridine (Up) at position 47 of tRNAs from thermophilic archaea. Up47 confers thermal stability and nuclease resistance to tRNAs. Atomic structures of native archaeal tRNA showed a unique metastable core structure stabilized by Up47. The 2′-phosphate of Up47 protrudes from the tRNA core and prevents backbone rotation during thermal denaturation. In addition, we identified the arkI gene, which encodes an archaeal RNA kinase responsible for Up47 formation. Structural studies showed that ArkI has a non-canonical kinase motif surrounded by a positively charged patch for tRNA binding. A knockout strain of arkI grew slowly at high temperatures and exhibited a synthetic growth defect when a second tRNA-modifying enzyme was depleted. We also identified an archaeal homologue of KptA as an eraser that efficiently dephosphorylates Up47 in vitro and in vivo. Taken together, our findings show that Up47 is a reversible RNA modification mediated by ArkI and KptA that fine-tunes the structural rigidity of tRNAs under extreme environmental conditions.

DOI: 10.1038/s41586-022-04677-2

Source: https://www.nature.com/articles/s41586-022-04677-2

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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