U1 AMO (antisense morpholino oligo) disrupts U1 snRNP structure to promote intronic premature cleavage and polyadenylation (PCPA)

• DOI: 10.1101/2023.02.24.529985
• Publication Date: 2023-02-26T02:25:11Z
• Authors: Qiumin Feng; Zejin Lin; Yanhui Deng; Yi Ran; Andy Peng Xiang; Congting Ye; Chengguo Yao
• Keywords: snRNP; RNA polymerase II; Transcription

Abstract Functional depletion of U1 snRNP with a 25 nt AMO (antisense morpholino oligonucleotides) may lead to intronic premature cleavage and polyadenylation (PCPA) thousands genes, phenomenon known as telescripting; however, the underlying mechanism remains elusive. In this study, we demonstrated that could disrupt structure both in vitro vivo, thereby affecting snRNP/RNAP polymerase II (RNAPII) interaction. We further showed treatment might promote RNAPII disassociation pre-mRNA an RNA pull-down assay. By performing ChIP-seq for phosphorylation Ser2 (Ser2P) Ser5 (Ser5P) C-terminal domain (CTD) (RNAPII), transcription elongation was disturbed upon treatment, particular high Ser2P signal at cryptic sites (PASs). addition, core 3’ processing factors CPSF/CstF are involved PAS. Their recruitment accumulated toward PASs indicated by iCLIP-seq analysis. Furthermore, most these PCPAed transcripts be exported cytoplasm have potential translated. Conclusively, our data provide more insight into telescripting, suggest common theme modulation important mode regulation mRNA polyadenylation.