Recognition of non-CpG repeats in Alu and ribosomal RNAs by the Z-RNA binding domain of ADAR1 induces A-Z junctions.
Recognition of non-CpG repeats in Alu and ribosomal RNAs by the Z-RNA binding domain of ADAR1 induces A-Z junctions.
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ADAR 1的Z-RNA结合结构域识别Alu和核糖体RNA中的非CpG重复序列诱导A-Z连接。
DOI：
10.1038/s41467-021-21039-0
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发表时间：
2021-02-04
影响因子：
16.6
通讯作者：
Vögeli B
中科院分区：
文献类型：
--
作者：
Nichols PJ;Bevers S;Henen M;Kieft JS;Vicens Q;Vögeli B
真核细胞rna的腺苷-肌苷（A-to-I）编辑对于防止自身免疫疾病至关重要。编辑由ADAR1进行，其先天免疫反应特异性细胞质异构体具有未知功能的Z-DNA结合域（Zα）。Zα还结合RNA中的CpG重复序列，这是Z-RNA形成的标志。出乎意料的是，Zα已经被预测-在某些情况下甚至被证明-结合到mRNA和rRNA中缺乏这种重复的特定区域。在这里，我们使用NMR，圆二色性和其他生物物理方法来证明和表征Zα与mRNA和rRNA片段的结合。我们的研究结果揭示了与Zα结合并采用Z-RNA构象的广泛RNA序列。结合伴随着邻近a形区域的不稳定，这与在B-Z-DNA连接中观察到的特征相似。Zα与非cpg序列的结合是特异性的，合作的，并且在低微摩尔范围内具有亲和力。这项工作使我们能够提出一个Zα如何影响ADAR1的RNA结合特异性的模型。ADAR1是一种干扰素诱导的酶，作为免疫反应的一部分，在转录组中催化腺嘌呤编辑为肌苷。在这里，作者建立了ADAR1如何识别非cpg RNA序列以促进A-Z连接的形成。
Adenosine-to-inosine (A-to-I) editing of eukaryotic cellular RNAs is essential for protection against auto-immune disorders. Editing is carried out by ADAR1, whose innate immune response-specific cytoplasmic isoform possesses a Z-DNA binding domain (Zα) of unknown function. Zα also binds to CpG repeats in RNA, which are a hallmark of Z-RNA formation. Unexpectedly, Zα has been predicted — and in some cases even shown — to bind to specific regions within mRNA and rRNA devoid of such repeats. Here, we use NMR, circular dichroism, and other biophysical approaches to demonstrate and characterize the binding of Zα to mRNA and rRNA fragments. Our results reveal a broad range of RNA sequences that bind to Zα and adopt Z-RNA conformations. Binding is accompanied by destabilization of neighboring A-form regions which is similar in character to what has been observed for B-Z-DNA junctions. The binding of Zα to non-CpG sequences is specific, cooperative and occurs with an affinity in the low micromolar range. This work allows us to propose a model for how Zα could influence the RNA binding specificity of ADAR1. ADAR1 is an interferon-induced enzyme that catalyzes editing of adenine to inosine across the transcriptome as part of the immune response. Here the authors establish how ADAR1 recognizes non-CpG RNA sequences to facilitate the formation of A-Z junctions.
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DOI：
10.1126/science.aac7442
发表时间：
2015-10-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hung T;Pratt GA;Sundararaman B;Townsend MJ;Chaivorapol C;Bhangale T;Graham RR;Ortmann W;Criswell LA;Yeo GW;Behrens TW
通讯作者：
Behrens TW
影响因子：
15
作者：
Kang, Young-Min;Bang, Jongchul;Lee, Joon-Hwa
通讯作者：
Lee, Joon-Hwa
DOI：
10.1073/pnas.240464097
发表时间：
2000-12-05
影响因子：
11.1
作者：
Brown, BA;Lowenhaupt, K;Rich, A
通讯作者：
Rich, A
影响因子：
14.9
作者：
Herbert, A;Schade, M;Rich, A
通讯作者：
Rich, A
影响因子：
12.3
作者：
Daniel C;Widmark A;Rigardt D;Öhman M
通讯作者：
Öhman M