Deadenylating RNA molecules Transfer RNA (tRNA) and messenger RNA molecules often acquire a terminal 2′,3′-cyclic phosphate group when processed in the cell. These cyclic phosphates provide attachment points for tRNA ligases and must be removed to recycle tRNAs from stalled ribosomes. Pinto et al. identified a deadenylase from human tissue culture cells that can do the job. Biochemical characterization and analysis of a crystal structure reveal ANGEL2 as a 2′,3′-cyclic phosphatase with functions for RNA processing and modification. Science, this issue p. 524 The RNA phosphatase ANGEL2 affects transfer RNA processing and unconventional messenger RNA splicing in human cells. RNA molecules are frequently modified with a terminal 2′,3′-cyclic phosphate group as a result of endonuclease cleavage, exonuclease trimming, or de novo synthesis. During pre-transfer RNA (tRNA) and unconventional messenger RNA (mRNA) splicing, 2′,3′-cyclic phosphates are substrates of the tRNA ligase complex, and their removal is critical for recycling of tRNAs upon ribosome stalling. We identified the predicted deadenylase angel homolog 2 (ANGEL2) as a human phosphatase that converts 2′,3′-cyclic phosphates into 2′,3′-OH nucleotides. We analyzed ANGEL2’s substrate preference, structure, and reaction mechanism. Perturbing ANGEL2 expression affected the efficiency of pre-tRNA processing, X-box–binding protein 1 (XBP1) mRNA splicing during the unfolded protein response, and tRNA nucleotidyltransferase 1 (TRNT1)–mediated CCA addition onto tRNAs. Our results indicate that ANGEL2 is involved in RNA pathways that rely on the ligation or hydrolysis of 2′,3′-cyclic phosphates.

中文翻译：

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ANGEL2 是 CCR4 脱腺苷酶家族的成员，具有 2',3'-环磷酸酶活性

去腺苷酸化 RNA 分子 转移 RNA (tRNA) 和信使 RNA 分子在细胞中加工时通常会获得末端 2',3'-环磷酸基团。这些环状磷酸盐为 tRNA 连接酶提供附着点，必须将其去除以从停滞的核糖体中回收 tRNA。平托等人。从人类组织培养细胞中鉴定出一种可以完成这项工作的脱腺苷酶。晶体结构的生化表征和分析表明 ANGEL2 是一种 2',3'-环状磷酸酶，具有 RNA 加工和修饰功能。科学，这个问题 p。524 RNA 磷酸酶 ANGEL2 影响人类细胞中的转移 RNA 加工和非常规信使 RNA 剪接。由于核酸内切酶切割、核酸外切酶修剪或从头合成，RNA 分子经常被末端 2',3'-环磷酸基团修饰。在预转移 RNA (tRNA) 和非常规信使 RNA (mRNA) 剪接过程中，2',3'-环磷酸盐是 tRNA 连接酶复合物的底物，它们的去除对于核糖体停滞时 tRNA 的再循环至关重要。我们将预测的脱腺苷酶天使同系物 2 (ANGEL2) 鉴定为一种人类磷酸酶，可将 2',3'-环磷酸酯转化为 2',3'-OH 核苷酸。我们分析了 ANGEL2 的底物偏好、结构和反应机制。扰乱 ANGEL2 表达会影响前 tRNA 加工的效率、X-box 结合蛋白 1 (XBP1) mRNA 在未折叠蛋白反应期间的剪接，以及 tRNA 核苷酸转移酶 1 (TRNT1) 介导的 CCA 添加到 tRNA 上。我们的结果表明 ANGEL2 参与依赖于 2',3'-环磷酸酯的连接或水解的 RNA 通路。