KDM5s are involved in selection of polyA sites. (A) Western blot and (B) RT-qPCR analyses of MCF7 cells treated with dimethyl sulfoxide (DMSO) or 10 μM KDM5-C70 for 3 days. The ratio of 3′UTR to CDS for CCND1 mRNA was plotted. Error bars represent SEM for biological triplicate experiments. (C) Western blot and (D) RT-qPCR analyses of HeLa cells treated with DMSO or 10 μM KDM5-C70 for 3 days. The ratio of 3′UTR to CDS for DICER1 mRNA was plotted. Error bars represent SEM for biological triplicate experiments. **P < 0.01. (E) RT-qPCR analysis of HeLa/iCas9-c1 cells transduced with lentiviruses carrying single-guide RNAs against KDM5A, KDM5B, KDM5C, or nontargeting control. The ratio of 3′UTR to CDS for DICER1 mRNA was plotted. KO, knockout. Error bars represent SEM for biological triplicate experiments. *P < 0.05; **P < 0.01. (F) Working model for KDM5 involvement in APA. KDM5 recruits the polyA machinery to nascent RNA to modulate polyA site choices. Demethylation or hydroxylation of certain subunits of the polyA machinery by KDM5 also contributes to selection of the polyA sites. The polyA sites (dashes) are noted on the nascent transcript.
To better understand how cancer initiates and spreads, Yale associate professor of pathology Qin Yan turned to epigenetics, which examines changes in the expression of genes and proteins that do not affect the underlying genetic codes. focused on a family of enzymes – KDM5 – that had been shown in previous studies to be involved in cancer cell growth and spreading.
Lauren Blair, an associate research scientist, conducted biochemical studies with Baker’s yeast as the model system, and identified an unexpected role of these enzymes in the process by which genetic messages are interpreted by yeast cells. Further studies showed that the enzymes’ role as regulators of this process is also important for human tumor cells to grow and spread. The finding could lead to a therapy that inhibits the enzyme, and tumor growth, in cancer patients.
http://advances.sciencemag.org/content/2/11/e1501662
http://yalecancercenter.org/news/article.aspx?id=14180
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