Regulation of translation by ribosomal RNA pseudouridylation.
Regulation of translation by ribosomal RNA pseudouridylation.
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DOI：
10.1126/sciadv.adg8190
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发表时间：
2023-08-18
期刊：
影响因子：
13.6
通讯作者：
Li, Hong
中科院分区：
文献类型：
--
作者：
Zhao, Yu;Rai, Jay;Li, Hong
假尿苷富含核糖体、剪接体、转移和信使 RNA，因此是中心法则的组成部分。然而，由于缺乏未经这种天然修饰的结构，假尿苷如何影响核糖体等分子装置的化学基础仍然难以捉摸。在这里，我们研究了由内部核糖体进入位点（IRES）元件启动的低假尿苷酸化核糖体的翻译。我们分析了多种功能状态下与陶拉综合征病毒 IRES 结合的核糖体的八种冷冻电子显微镜结构。我们发现通过水和长程碱基配对的假尿苷介导的相互作用普遍丧失。在转位酶、真核延伸因子 2 和鸟苷 5'-三磷酸水解存在的情况下，低假尿苷酸化核糖体有利于罕见的不利于解码的构象，该构象在 P 位点尿苷仍被修饰的核糖体群体中部分恢复。学到的结构原理建立了功能缺陷和修饰损失之间的联系，并且可能适用于其他假尿苷相关过程。核糖体RNA修饰对核糖体的结构和功能具有深远的影响。
Pseudouridine is enriched in ribosomal, spliceosomal, transfer, and messenger RNA and thus integral to the central dogma. The chemical basis for how pseudouridine affects the molecular apparatus such as ribosome, however, remains elusive owing to the lack of structures without this natural modification. Here, we studied the translation of a hypopseudouridylated ribosome initiated by the internal ribosome entry site (IRES) elements. We analyzed eight cryo–electron microscopy structures of the ribosome bound with the Taura syndrome virus IRES in multiple functional states. We found widespread loss of pseudouridine-mediated interactions through water and long-range base pairings. In the presence of the translocase, eukaryotic elongation factor 2, and guanosine 5′-triphosphate hydrolysis, the hypopseudouridylated ribosome favors a rare unconducive conformation for decoding that is partially recouped in the ribosome population that remains modified at the P-site uridine. The structural principles learned establish the link between functional defects and modification loss and are likely applicable to other pseudouridine-associated processes. Ribosomal RNA modifications have a profound impact on the structure and function of ribosomes.
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影响因子：
48
作者：
Kucukelbir, Alp;Sigworth, Fred J.;Tagare, Hemant D.
通讯作者：
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影响因子：
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作者：
Hassan, Asem;Byju, Sandra;Freitas, Frederico Campos;Roc, Claude;Pender, Nisaa;Nguyen, Kien;Kimbrough, Evelyn M.;Mattingly, Jacob M.;Gonzalez, Ruben L.;de Oliveira, Ronaldo Junio;Dunham, Christine M.;Whitford, Paul C.
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作者：
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DOI：
10.1182/asheducation-2011.1.480
发表时间：
2011-12-01
期刊：
HEMATOLOGY-AMERICAN SOCIETY HEMATOLOGY EDUCATION PROGRAM
影响因子：
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作者：
Dokal, Inderjeet
通讯作者：
Dokal, Inderjeet
影响因子：
14.9
作者：
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通讯作者：
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