高通量测序技术在肿瘤的RNA可变剪接和选择性多聚腺苷酸化研究中的应用OA

Alternative splicing(AS)and alternative polyadenylation(APA)constitute pivotal post-transcriptional regulatory mechanisms in eukaryotes.By generating diverse mRNA isoforms,they substantially enhance the complexity of gene expression and proteomic diversity,playing critical roles in cellular physiological and pathological processes particularly exerting profound impacts on tumor initiation and progression.The advent of high-throughput sequencing technologies has empowered large-scale investigations of AS and APA events.Due to its limitations in read length,conventional second-generation sequencing(NGS)is difficult to accurately analyze complex and variable splicing patterns and APA sites.The third-generation sequencing technology has the characteristics of long read length and can effectively solve this problem.This review synthesizes advances in applying NGS and long-read sequencing(LRS)to characterize tumor-associated RNA alternative splicing and alternative polyadenylation events.Literature analysis demonstrates the significant potential of long-read sequencing in oncology research.Compared to NGS,LRS enables more accurate identification of complex alternative splicing patterns,precise mapping of splice sites and APA sites,and resolution of complete transcript isoform structures,facilitating the discovery of novel tumor-specific splicing variants and APA events.Long-read sequencing technology paves new path for comprehensively mapping AS/APA landscapes in tumors and elucidating their mechanistic roles in tumorigenesis.Future applications hold promise for discovering novel tumor diagnostic biomarkers,prognostic indicators,and developing precision therapeutic strategies targeting RNA splicing regulation.