Fault-Tolerance Study on a Positive-Charged Cleft in 18S rRNA Methyltransferase DIMT1.

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemistry Biochemistry Pub Date : 2025-01-21 Epub Date: 2025-01-06 DOI:10.1021/acs.biochem.4c00319
Xiaoyu Wei, Nora Sampson, Sarai Maria Figueroa Mendoza, Yulia Gonskikh, Kathy Fange Liu
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Abstract

Dimethyladenosine transferase 1 (DIMT1) is an RNA N6,6-dimethyladenosine (m26,6A) methyltransferase. DIMT1's role in pre-rRNA processing and ribosome biogenesis is critical for cell proliferation. Here, we investigated the minimal number of residues in a positively charged cleft on DIMT1 required for cell proliferation. We demonstrate that a minimum of four residues in the positively charged cleft must be mutated to alter DIMT1's RNA-binding ability. The variant (4mutA-DIMT1), which presents reduced RNA binding affinity, is diffuse in the nucleoplasm and nucleolus, in contrast with the primarily nucleolar localization of wild-type DIMT1. The aberrant cellular localization significantly impaired 4mutA-DIMT1's role in supporting cell proliferation, as shown in competition-based cell proliferation assays. These results identify the minimum region in DIMT1 to target for cell proliferation regulation.

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18S rRNA甲基转移酶DIMT1中一个正电荷裂缝的容错研究
二甲基腺苷转移酶1 (DIMT1)是一种RNA n6,6 -二甲基腺苷(m26,6a)甲基转移酶。DIMT1在前rrna加工和核糖体生物发生中的作用对细胞增殖至关重要。在这里,我们研究了细胞增殖所需的DIMT1正电荷间隙中残基的最小数量。我们证明了至少四个残基在带正电的间隙中必须发生突变才能改变DIMT1的rna结合能力。与野生型DIMT1的主要核仁定位相比,变异(4mutA-DIMT1)在核质和核仁中弥漫性分布,其RNA结合亲和力降低。基于竞争的细胞增殖实验显示,异常的细胞定位显著削弱了4mutA-DIMT1在支持细胞增殖中的作用。这些结果确定了DIMT1中用于细胞增殖调控的最小目标区域。
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来源期刊
Biochemistry Biochemistry
Biochemistry Biochemistry 生物-生化与分子生物学
CiteScore
5.50
自引率
3.40%
发文量
336
审稿时长
1-2 weeks
期刊介绍: Biochemistry provides an international forum for publishing exceptional, rigorous, high-impact research across all of biological chemistry. This broad scope includes studies on the chemical, physical, mechanistic, and/or structural basis of biological or cell function, and encompasses the fields of chemical biology, synthetic biology, disease biology, cell biology, nucleic acid biology, neuroscience, structural biology, and biophysics. In addition to traditional Research Articles, Biochemistry also publishes Communications, Viewpoints, and Perspectives, as well as From the Bench articles that report new methods of particular interest to the biological chemistry community.
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