Abstract
Human PUF-A/PUM3 is a RNA and DNA binding protein participating in the nucleolar processing of 7S to 5.8S rRNA. The nucleolar localization of PUF-A redistributes to the nucleoplasm upon the exposure to genotoxic agents in cells. However, little is known regarding the roles of PUF-A in tumor progression. Phosphoprotein database analysis revealed that Y259 phosphorylation of PUF-A is the most prevalent residue modified. Here, we reported the importance of PUF-A’s phosphorylation on Y259 in tumorigenesis. PUF-A gene was knocked out by the Crispr/Cas9 method in human cervix epithelial HeLa cells. Loss of PUF-A in HeLa cells resulted in reduced clonogenic and lower transwell invasion capacity. Introduction of PUF-AY259F to PUF-A deficient HeLa cells was unable to restore colony formation. In addition, the unphosphorylated mutant of PUF-A, PUF-AY259F, attenuated PUF-A protein stability. Our results suggest the important role of Y259 phosphorylation of PUF-A in cell proliferation.
Highlights
Pumilio/fem-3 (PUF) proteins belong to the members of Drosophila melanogaster Pumilio and Caenorhabditis elegans fem-3 mRNA binding factors [1,2], which contain of 8–12 conserved α-helical Pumilio (PUM) repeats [3,4]
To investigate the roles of PUF-A in cancer progression, we examined the association of the PUF-A expression level with overall survival in cancer patients
Using the Kaplan Meier Plotter [19], a publicly accessible database, a high level of PUF-A mRNA is noticeably associated with poor survival in cervical squamous carcinoma, liver hepatocellular carcinoma, pancreatic ductal adenocarcinoma, esophageal adenocarcinoma and kidney renal clear cell carcinoma (Fig 1A-1E)
Summary
Pumilio/fem-3 (PUF) proteins belong to the members of Drosophila melanogaster Pumilio and Caenorhabditis elegans fem-3 mRNA binding factors [1,2], which contain of 8–12 conserved α-helical Pumilio (PUM) repeats [3,4]. In each PUM repeat, there are three α helices and the second α helix contains the tripartite recognition motif (TRM) that recognizes a specific RNA base [5,6,7,8,9]. PUF-A ( known as PUM3, Pumilio RNA binding family member 3, an ortholog of yeast Puf6) recognizes structured RNA and participates in pre-ribosomal RNA processing [10,11]. Ribosome biogenesis requires hundreds of factors in the processing of ribosomal RNAs and assembly of rRNAs and ribosomal proteins into the large ribonucleoprotein
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