title: Loss of the RNA helicase SKIV2L2 impairs mitotic progression and replication-dependent histone mRNA turnover in murine cell lines.
abstract: RNA surveillance via the nuclear exosome requires cofactors such as the helicase SKIV2L2 to process and degrade certain noncoding RNAs. This research aimed to characterize the phenotype associated with RNAi knockdown ofSkiv2l2in two murine cancer cell lines: Neuro2A and P19. SKIV2L2 depletion in Neuro2A and P19 cells induced changes in gene expression indicative of cell differentiation and reduced cellular proliferation by 30%. Propidium iodide-based cell-cycle analysis ofSkiv2l2knockdown cells revealed defective progression through the G2/M phase and an accumulation of mitotic cells, suggesting SKIV2L2 contributes to mitotic progression. Since SKIV2L2 targets RNAs to the nuclear exosome for processing and degradation, we identified RNA targets elevated in cells depleted of SKIV2L2 that could account for the observed twofold increase in mitotic cells.Skiv2l2knockdown cells accumulated replication-dependent histone mRNAs, among other RNAs, that could impede mitotic progression and indirectly trigger differentiation.
authors.affiliation: Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin 53201, USA.
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Onderak
authors.affiliation: Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin 53201, USA.
authors.forename: James T
authors.initials: JT
authors.lastname: Anderson
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D004261:DNA Replication; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006657:Histones / Q000235:genetics*; D051379:Mice; D008938:Mitosis / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics; D020365:RNA Helicases; D034622:RNA Interference; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics
chemical_list: D006657:Histones; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D020365:RNA Helicases; C569190:SKIV2L2 protein, mouse
keywords: RNA surveillance; RNA turnover; TRAMP complex; histones