glycogen synthase kinase 3 beta (gsk3β) phosphorylates the rnaase iii enzyme drosha at s300 and s302糖原合成酶激酶3β(gsk3β)磷酸化核糖核酸酶iii酶drosha s300和s302.pdfVIP

Glycogen Synthase Kinase 3 Beta (GSK3b) Phosphorylates the RNAase III Enzyme Drosha at S300 and S302 Xiaoli Tang, Ming Li, Lynne Tucker, Bharat Ramratnam* Department of Medicine, Warren Alpert Medical School of Brown University, Providence, Rhode Island, United States of America Abstract The canonical microRNA (miRNA) pathway commences with the enzymatic cleavage of the primary gene transcript (pri- miRNA) by the RNAase III enzyme Drosha in the nucleus into shorter pre-miRNA species that are subsequently exported to the cytoplasm for further processing into shorter, mature miRNA molecules. Using a series of reporter constructs, we have previously demonstrated that phosphorylation of Drosha at Ser 300 and 302 was required for its nuclear localization. Here, we identify GSK3b as the culprit kinase. We demonstrate that Drosha is unable to selectively localize to the nucleus in cells deficient in GSK3b. These findings expand the substrate base of GSK3b to include a central component of the miRNA biogenesis pathway. Citation: Tang X, Li M, Tucker L, Ramratnam B (2011) Glycogen Synthase Kinase 3 Beta (GSK3 b) Phosphorylates the RNAase III Enzyme Drosha at S300 and S302. PLoS ONE 6(6): e20391. doi:10.1371/journal.pone.0020391 ´ ´ Editor: Jean-Luc E. P. H. Darlix, Institut National de la Sante et de la Recherche Medicale, France Received January 25, 2011; Accepted May 2, 2011; Published June 3, 2011 Copyright: 2011 Tang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by National Institutes of Health (NIH) (P20RR025179 and R01AI058697)