Pervasive functional translation of noncanonical human open reading frames
Pervasive functional translation of noncanonical human open reading frames
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DOI：
10.1126/science.aay0262
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发表时间：
2020-03-06
期刊：
影响因子：
56.9
通讯作者：
Weissman, Jonathan S.
中科院分区：
文献类型：
--
作者：
Chen, Jin;Brunner, Andreas-David;Weissman, Jonathan S.
核糖体分析揭示了普遍的，但在很大程度上未表征的翻译以外的规范编码序列（CDS）。在这项工作中，我们利用一种基于CRISPR的系统性筛选策略来识别数百种对细胞生长至关重要的非经典CDS，这些CDS的破坏会导致人类细胞中特异性、稳健的转录组学和表型变化。编码的微蛋白的功能表征揭示了不同的细胞定位，特异性蛋白结合伴侣，和数百种微蛋白，由人类白细胞抗原系统。我们发现多个微蛋白编码的上游开放阅读框架，形成稳定的复合物与主要的，典型的蛋白编码的相同的信使RNA，从而揭示了使用功能性双顺反子操纵子在哺乳动物中。总之，我们的研究结果指向一个功能性人类微蛋白家族，它们在细胞中发挥着重要而多样的作用。
Ribosome 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.