P53-induced RNA-binding protein ZMAT3 is splicing regulator that inhibits the splicing of oncogenic CD44 variants in CRC [PAR-CLIP_ZMAT3]

ABSTRACT: Purpose: p53 is a well-studied protein in which the activation of its main targets is not enough to explain its tumor suppressor effect. Aiming to search for direct p53 targets that mediate less studied processes within p53 pathway, like post-transcriptional regulation, we selected ZMAT3 as the RNA-binding protein most upregulated by p53 activation. Methods: We investigated ZMAT3 targets by using PAR-CLIP and RNA-seq in colorectal cancer cell line HCT116. Results: We found that ZMAT3 binds to ~5000 genes mainly in their introns. It also causes alternative splicing and CD44 was its mostly altered target. ZMAT3 knock-down increased CD44v2-v10 and CD44v3-v10, but decreased CD44s expression. Increased survival and clonogenicity was observed upon knock-down of ZMAT3, which was rescued upon concurrent knock-down of CD44v Conclusions: We propose that ZMAT3 regulates splicing of CD44 following activation by p53, which upregulates CD44s at the expense of CD44v isoforms and leads to a decrease tumorigenicity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE150715 | GEO | 2020/12/18

REPOSITORIES: GEO