title: hnRNP Q regulates Cdc42-mediated neuronal morphogenesis.
abstract: The RNA-binding protein hnRNP Q has been implicated in neuronal mRNA metabolism. Here, we show that knockdown of hnRNP Q increased neurite complexity in cultured rat cortical neurons and induced filopodium formation in mouse neuroblastoma cells. Reexpression of hnRNP Q1 in hnRNP Q-depleted cells abrogated the morphological changes of neurites, indicating a specific role for hnRNP Q1 in neuronal morphogenesis. A search for mRNA targets of hnRNP Q1 identified functionally coherent sets of mRNAs encoding factors involved in cellular signaling or cytoskeletal regulation and determined its preferred binding sequences. We demonstrated that hnRNP Q1 bound to a set of identified mRNAs encoding the components of the actin nucleation-promoting Cdc42/N-WASP/Arp2/3 complex and was in part colocalized with Cdc42 mRNA in granules. Using subcellular fractionation and immunofluorescence, we showed that knockdown of hnRNP Q reduced the level of some of those mRNAs in neurites and redistributed their encoded proteins from neurite tips to soma to different extents. Overexpression of dominant negative mutants of Cdc42 or N-WASP compromised hnRNP Q depletion-induced neurite complexity. Together, our results suggest that hnRNP Q1 may participate in localization of mRNAs encoding Cdc42 signaling factors in neurites, and thereby may regulate actin dynamics and control neuronal morphogenesis.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Hung-Hsi
authors.initials: HH
authors.lastname: Chen
authors.forename: Hsin-I
authors.initials: HI
authors.lastname: Yu
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Chiang
authors.forename: Yu-De
authors.initials: YD
authors.lastname: Lin
authors.forename: Ben-Chang
authors.initials: BC
authors.lastname: Shia
authors.forename: Woan-Yuh
authors.initials: WY
authors.lastname: Tarn
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development; D055785:Gene Knockdown Techniques; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism*; D051379:Mice; D009024:Morphogenesis / Q000502:physiology; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C486049:Syncrip protein, mouse; C530621:hnRNPQ protein, rat; D020764:cdc42 GTP-Binding Protein