TY - JOUR A1 - Hussain, Shobbir A1 - Benavente, Sandra Blanco A1 - Nascimento, Elisabete A1 - Dragoni, Ilaria A1 - Kurowski, Agata A1 - Gillich, Astrid A1 - Humphreys, Peter A1 - Frye, Michaela T1 - The nucleolar RNA methyltransferase Misu (NSun2) is required for mitotic spindle stability T2 - The journal of cell biology N2 - Myc-induced SUN domain–containing protein (Misu or NSun2) is a nucleolar RNA methyltransferase important for c-Myc–induced proliferation in skin, but the mechanisms by which Misu contributes to cell cycle progression are unknown. In this study, we demonstrate that Misu translocates from the nucleoli in interphase to the spindle in mitosis as an RNA–protein complex that includes 18S ribosomal RNA. Functionally, depletion of Misu caused multiple mitotic defects, including formation of unstructured spindles, multipolar spindles, and chromosome missegregation, leading to aneuploidy and cell death. The presence of both RNA and Misu is required for correct spindle assembly, and this process is independent of active translation. Misu might mediate its function at the spindle by recruiting nucleolar and spindle-associated protein (NuSAP), an essential microtubule-stabilizing and bundling protein. We further identify NuSAP as a novel direct target gene of c-Myc. Collectively, our results suggest a novel mechanism by which c-Myc promotes proliferation by stabilizing the mitotic spindle in fast-dividing cells via Misu and NuSAP. Y1 - 2009 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/7370 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30-70098 N1 - © 2009 Hussain et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). VL - 186 IS - 1 SP - 27 EP - 40 ER -