程序性核糖体-1位移码(-1PRF)是一种翻译重编码机制，在所有生物中均存在。翻译过程中，部分核糖体遇到移码信号后后退一个核苷酸，沿新读码框继续翻译，生成C端不同的两种蛋白。除了翻译重编码，-1PRF还调控真核mRNA稳定性，是一种重要的基因表达调控模式。生物信息学预测，高等真核细胞中可能多达10%的基因含有-1PRF序列，但仅有有限几个报道，众多此类基因亟待鉴定。最近我们发现细胞因子Shiftless (SFL)特异结合含-1PRF信号的mRNA，抑制移码过程，为-1PRF基因的鉴定提供了新工具。本项目将利用紫外交联免疫沉淀技术（CLIP）鉴定与SFL互作mRNA；结合生物信息学预测，鉴定潜在-1PRF基因；在细胞水平确认-1PRF的发生及对SFL敏感性；利用SFL敲除小鼠分析其对特定-1PRF基因（优选免疫相关基因）的调控和表型。该研究有助于了解SFL如何通过抑制-1PRF而发挥功能。

Programmed ribosomal frameshifting（-1PRF） is an important translation recoding mechanism, which was first found in viruses and exists in all domains of life. Translating ribosomes pause at -1PRF signal. While most ribosomes move on in the original reading frame, a small proportion slip back one nucleotide to translate in a new frame, resulting in two protein products differing at the C-termini. In eukaryotes, -1PRF can also result in a premature stop codon, which would lead to the degradation of the mRNA, serving as a novel mechanism for posttranscriptional regulation of gene expression. It is predicted that up to 10% eukaryote genes might harbor -1PRF signals. However, only very few of such genes have been reported. A large number of -1PRF genes remain to be identified. Very recently，we reported that cellular protein Shiftless (SFL) is a broad-spectrum inhibitor of -1PRF through binding to the translating ribosomes and -1PRF signal of mRNA simultaneously. In this project, Gel-omitted Ligation-dependent CLIP（Gold-CLIP) will be employed to identify SFL-interacting mRNAs in human and mouse cells. In combination with the potential -1PRF gene library predicted by bioinformatics analysis, more -1PRF genes will be identified. The candidate -1PRF genes and their sensitivity to SFL will be confirmed in cell lines. With SFL gene knockout mice, we will explore whether the expressions of these genes are regulated in vivo and the resulting phenotypes. This project will identify new -1PRF containing genes and help to understand the biological function of SFL.