U1A is a positive regulator of the expression of heterologous and cellular genes involved in cell proliferation and migration
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Eric Rovira Beatriz Moreno Nerea Razquin Roland Hjerpe Monika Gonzalez-Lopez Rosa Barrio Igor Ruiz De Los Mozos Jernej Ule Fernando Pastor Lorea Blazquez Puri FortesAbstract
Here, we show that direct recruitment of U1A to target transcripts can increase gene expression. This is a new regulatory role, in addition to previous knowledge showing that U1A decreases the levels of U1A mRNA and other specific targets. In fact, genome-wide, U1A more often increases rather than represses gene expression and many U1A-upregulated transcripts are directly bound by U1A according to individual nucleotide resolution crosslinking and immunoprecipitation (iCLIP) studies. Interestingly, U1A-mediated positive regulation can be transferred to a heterologous system for biotechnological purposes. Finally, U1A-bound genes are enriched for those involved in cell cycle and adhesion. In agreement with this, higher U1A mRNA expression associates with lower disease-free survival and overall survival in many cancer types, and U1A mRNA levels positively correlate with those of some oncogenes involved in cell proliferation. Accordingly, U1A depletion leads to decreased expression of these genes and the migration-related gene /CTGF, which shows the strongest regulation by U1A. A decrease in U1A causes a strong drop in expression and CTGF secretion and defects in the expression of CTGF EMT targets, cell migration, and proliferation. These results support U1A as a putative therapeutic target for cancer treatment. In addition, U1A-binding sequences should be considered in biotechnological applications.
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Volume 28
Pages 831-846
Available online
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Publisher website (DOI) 10.1016/j.omtn.2022.05.023
Europe PubMed Central 35664701
Pubmed 35664701
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