State Key Laboratory for Conservation and Utilization of Bio-Resource in Yunnan, Key Laboratory for Southwest Microbial Diversity of the Ministry of Education, Yunnan Key Laboratory of Cell Metabolism and Diseases, Center for Life Science, School of Life Sciences, Yunnan University, Kunming 650021, China.
Southwest United Graduate School, Kunming650092, China.
Nucleic Acids Res. 2024 Mar 21;52(5):2463-2479. doi: 10.1093/nar/gkae035.
Ribosomal frameshifting refers to the process that ribosomes slip into +1 or -1 reading frame, thus produce chimeric trans-frame proteins. In viruses and bacteria, programmed ribosomal frameshifting can produce essential trans-frame proteins for viral replication or regulation of other biological processes. In humans, however, functional trans-frame protein derived from ribosomal frameshifting is scarcely documented. Combining multiple assays, we show that short codon repeats could act as cis-acting elements that stimulate ribosomal frameshifting in humans, abbreviated as CRFS hereafter. Using proteomic analyses, we identified many putative CRFS events from 32 normal human tissues supported by trans-frame peptides positioned at codon repeats. Finally, we show a CRFS-derived trans-frame protein (HDAC1-FS) functions by antagonizing the activities of HDAC1, thus affecting cell migration and apoptosis. These data suggest a novel type of translational recoding associated with codon repeats, which may expand the coding capacity of mRNA and diversify the regulation in human.
核糖体移码是指核糖体滑入+1 或-1 读框，从而产生嵌合跨框蛋白。在病毒和细菌中，程序性核糖体移码可以产生病毒复制或调节其他生物过程所必需的跨框蛋白。然而，在人类中，很少有功能跨框蛋白来源于核糖体移码。我们结合多种检测方法，证明短密码子重复序列可以作为顺式作用元件，刺激人类核糖体移码，简称为 CRFS。通过蛋白质组学分析，我们从 32 个人体正常组织中鉴定到许多潜在的 CRFS 事件，这些事件都有位于密码子重复序列处的跨框肽。最后，我们发现一个 CRFS 衍生的跨框蛋白（HDAC1-FS）通过拮抗 HDAC1 的活性来发挥作用，从而影响细胞迁移和凋亡。这些数据表明，一种与密码子重复序列相关的新型翻译重编码可能会扩展 mRNA 的编码能力，并使人类的调控多样化。
