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U1 snRNP regulates cancer cell migration and invasion

Oh J-M, Venters CC, Di C, Pinto AM, Wan L, Younis I, Cai Z, Arai C, So BR, Dreyfuss G
bioRxiv. 2019;[preprint] doi:10.1101/730515
Stimulated cells and cancer cells have widespread shortening of mRNA 3′-utranslated regions (3′UTRs) and switches to shorter mRNA isoforms due to usage of more proximal polyadenylation signals (PASs) in the last exon and in introns. U1 snRNA (U1), vertebrates′ most abundant non-coding (spliceosomal) small nuclear RNA, silences proximal PASs and its inhibition with antisense morpholino oligonucleotides (U1 AMO) triggers widespread mRNA shortening. Here we show that U1 AMO also modulates cancer cells′ phenotype, dose-dependently increasing migration and invasion in vitro by up to 500%, whereas U1 over-expression has the opposite effect. In addition to 3′UTR length, numerous transcriptome changes that could contribute to this phenotype are observed, including alternative splicing, and mRNA expression levels of proto-oncogenes and tumor suppressors. These findings reveal an unexpected link between U1 regulation and oncogenic and activated cell states, and suggest U1 as a potential target for their modulation.
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cell culture: HeLa, A549, MCF-7 and MB-231
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