SNORD18B/SNORD18C-RPL23A promotes homologous recombination repair by regulating BRCA1 translation in colorectal cancer cells

作者：Chuxian Lin, Junyan He, Lei Wu, Xin Liu, Ying Fan, Dan Cai, Meng Jia, Wencheng Zhang, Qi Wang, Yaqiong Li, Ruixue Liu, Wenqing Lu, Jianan Ma, Zhu Maoxiang, Pingkun Zhou, Zhenhua Qi, Liping Shen, Zhidong Wang · 发表于：Cell Death Discovery · 年份：2026 · DOI：10.1038/s41420-026-03289-3 · 研究领域：RNA modifications and cancer、DNA Repair Mechanisms、PARP inhibition in cancer therapy

Abstract Homologous recombination (HR) is one of the classical pathways for repairing DNA double-strand breaks (DSBs), a type of lesion that poses a severe threat to genomic stability and cell survival. The role of small nucleolar RNAs (snoRNAs), particularly their interactions with ribosomal proteins, in the HR repair has not been reported. This is the first study to report the role of snoRNA genes SNORD18B and SNORD18C ( SNORD18B/C ) in HR repair, demonstrating that they exert an oncogenic function in colorectal cancer (CRC) by promoting cell proliferation and radioresistance. Mechanistically, SNORD18B/C directly interacts with the ribosomal protein RPL23A to enhance the translation of BRCA1 independent of the canonical 2′-O-methylation of 28S rRNA, thereby promoting HR efficiency to facilitate radiation-induced DSB repair. Collectively, our findings confirm that the SNORD18B/C -RPL23A-BRCA1 axis is crucial for HR repair and highlight the SNORD18B/C as potential CRC therapeutic targets.