This study investigates the role of U1 snRNP in regulating cancer cell migration and invasion. U1 snRNP, a key component of the spliceosome, influences mRNA processing by silencing proximal polyadenylation sites (PASs). When U1 snRNP is inhibited using antisense morpholino oligonucleotides (U1 AMO), it leads to widespread premature transcription termination and mRNA shortening. The study shows that low doses of U1 AMO significantly enhance cancer cell migration and invasion by up to 500%, while U1 overexpression has the opposite effect. These effects are accompanied by various transcriptome changes, including alternative splicing and altered expression of proto-oncogenes and tumor suppressors. The findings suggest that U1 homeostasis plays a critical role in oncogenic and activated cell states, and U1 could be a potential target for modulating these states. The study also reveals that U1 level changes affect 3'UTR lengths and mRNA isoforms, which can influence cancer progression by altering miRNA binding sites and other regulatory elements. The results highlight the importance of U1 in maintaining normal gene expression balance and preventing the activation of multiple oncogenic drivers. The study provides insights into the complex interplay between U1 snRNP and mRNA processing in cancer cells.This study investigates the role of U1 snRNP in regulating cancer cell migration and invasion. U1 snRNP, a key component of the spliceosome, influences mRNA processing by silencing proximal polyadenylation sites (PASs). When U1 snRNP is inhibited using antisense morpholino oligonucleotides (U1 AMO), it leads to widespread premature transcription termination and mRNA shortening. The study shows that low doses of U1 AMO significantly enhance cancer cell migration and invasion by up to 500%, while U1 overexpression has the opposite effect. These effects are accompanied by various transcriptome changes, including alternative splicing and altered expression of proto-oncogenes and tumor suppressors. The findings suggest that U1 homeostasis plays a critical role in oncogenic and activated cell states, and U1 could be a potential target for modulating these states. The study also reveals that U1 level changes affect 3'UTR lengths and mRNA isoforms, which can influence cancer progression by altering miRNA binding sites and other regulatory elements. The results highlight the importance of U1 in maintaining normal gene expression balance and preventing the activation of multiple oncogenic drivers. The study provides insights into the complex interplay between U1 snRNP and mRNA processing in cancer cells.