非典型人類開放閱讀框的功能
作者:
小柯機器人發布時間:2020/3/18 13:36:49
美國加州大學Jonathan S. Weissman研究組在研究中取得進展。他們發現非典型人類開放閱讀框的普遍翻譯功能。這一研究成果發表在2020年3月6日出版的《科學》雜誌上。
在這項工作中,研究人員利用基於CRISPR的系統篩選策略鑑定了數百種非典型-典型編碼序列(CDS),這些CDS對細胞生長至關重要,並且破壞這些序列會引起人細胞中特定的、強烈的轉錄組和表型變化。編碼微蛋白的功能分析揭示了不同細胞定位、特定蛋白結合伴侶和由人類白細胞抗原呈遞的數百種微蛋白。研究發現在上遊開放閱讀框中編碼的多種微蛋白,它們與編碼在同一信使RNA上主要的典型蛋白質形成穩定複合物,從而揭示了哺乳動物中功能性雙順反子操縱子的使用。總之,這些結果揭示了一系列功能重要的人類微蛋白,它們在細胞中起著至關重要的作用。
據悉,核糖體分析揭示了典型編碼序列(CDSs)之外的普遍但很多無典型特徵的翻譯。
附:英文原文
Title: Pervasive functional translation of noncanonical human open reading frames
Author: Jin Chen, Andreas-David Brunner, J. Zachery Cogan, James K. Nuez, Alexander P. Fields, Britt Adamson, Daniel N. Itzhak, Jason Y. Li, Matthias Mann, Manuel D. Leonetti, Jonathan S. Weissman
Issue&Volume: 2020/03/06
Abstract: AbstractRibosome profiling has revealed pervasive but largely uncharacterized translation outside of canonical coding sequences (CDSs). In this work, we exploit a systematic CRISPR-based screening strategy to identify hundreds of noncanonical CDSs that are essential for cellular growth and whose disruption elicits specific, robust transcriptomic and phenotypic changes in human cells. Functional characterization of the encoded microproteins reveals distinct cellular localizations, specific protein binding partners, and hundreds of microproteins that are presented by the human leukocyte antigen system. We find multiple microproteins encoded in upstream open reading frames, which form stable complexes with the main, canonical protein encoded on the same messenger RNA, thereby revealing the use of functional bicistronic operons in mammals. Together, our results point to a family of functional human microproteins that play critical and diverse cellular roles.
DOI: 10.1126/science.aay0262
Source: https://science.sciencemag.org/content/367/6482/1140
Science:《科學》,創刊於1880年。隸屬於美國科學促進會,最新IF:41.037