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Mounting studies suggest that the protein-coding potential of the human genome is underestimated, and previously unannotated open reading frames (ORFs) have been revealed with technological advances. Although the coding potential of many non-canonical ORFs (ncORFs) is now recognized, their functional prevalence remains to be characterized, partly due to the technical difficulty and labour intensity in screening numerous ncORFs at once. Here, we describe a gain-of-function genomic screen to identify functional ncORF-encoded proteins responsible for breast cancer tumorigenesis. This method is thought to improve the efficiency of characterizing previously neglected ncORFs and reveal potential targets for cancer treatment.

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Gain-of-Functional Genomic Screening for Microproteins Essential for Tumorigenesis

  • 实验方案

  • 发表日期：

    2026年

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  • Anni Ge,
  • Yuan Gao,
  • Xiaolong Yang

摘要

Mounting studies suggest that the protein-coding potential of the human genome is underestimated, and previously unannotated open reading frames (ORFs) have been revealed with technological advances. Although the coding potential of many non-canonical ORFs (ncORFs) is now recognized, their functional prevalence remains to be characterized, partly due to the technical difficulty and labour intensity in screening numerous ncORFs at once. Here, we describe a gain-of-function genomic screen to identify functional ncORF-encoded proteins responsible for breast cancer tumorigenesis. This method is thought to improve the efficiency of characterizing previously neglected ncORFs and reveal potential targets for cancer treatment.