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CCR4腺苷酸酶家族的成员ANGEL2具有2',3'-环磷酸酶活性
2020-08-01 23:48

奥地利维也纳医科大学Javier Martinez和Stefan Weitzer研究团队合作取得一项新突破。他们的最新研究发现ANGEL2是CCR4腺苷酸酶家族的成员,具有2',3'-环磷酸酶活性。 这一研究成果于2020年7月31日发表在国际学术期刊《科学》杂志上。

研究人员发现假定的腺苷酸酶angel同源物2(ANGEL2)是人体内的磷酸酶,可将2',3'-环状磷酸酯转化为2',3'-OH核苷酸。研究人员分析了ANGEL2的底物偏好性、结构和反应机理。干扰ANGEL2的表达会影响前转运RNA(tRNA)的加工效率、未折叠蛋白反应过程中X-box结合蛋白1(XBP1)信使RNA(mRNA)的剪接以及tRNA核苷酸转移酶1(TRNT1)介导CCA进入tRNA的效率。该结果表明ANGEL2参与了依赖2',3'-环状磷酸酯连接或水解的RNA途径。

据介绍,由于核酸内切酶切割、核酸外切酶修整或从头合成,RNA分子末端经常被2',3'-磷酸环基团修饰。在前tRNA和非典型mRNA剪接过程中,2',3'-环状磷酸酯是tRNA连接酶复合物的底物,它们的去除对于核糖体失速后tRNA的回收至关重要。

附:英文原文

Title: ANGEL2 is a member of the CCR4 family of deadenylases with 2′,3′-cyclic phosphatase activity

Author: Paola H. Pinto, Alena Kroupova, Alexander Schleiffer, Karl Mechtler, Martin Jinek, Stefan Weitzer, Javier Martinez

Issue&Volume: 2020/07/31

Abstract: 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.

DOI: 10.1126/science.aba9763

Source: https://science.sciencemag.org/content/369/6503/524

Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037
官方网址:https://www.sciencemag.org/
投稿链接:https://cts.sciencemag.org/scc/#/login

本期文章:《科学》:Volume 369 Issue 6503

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