title: Negative regulation of RhoA translation and signaling by hnRNP-Q1 affects cellular morphogenesis.
abstract: The small GTPase RhoA has critical functions in regulating actin dynamics affecting cellular morphogenesis through the RhoA/Rho kinase (ROCK) signaling cascade. RhoA signaling controls stress fiber and focal adhesion formation and cell motility in fibroblasts. RhoA signaling is involved in several aspects of neuronal development, including neuronal migration, growth cone collapse, dendrite branching, and spine growth. Altered RhoA signaling is implicated in cancer and neurodegenerative disease and is linked to inherited intellectual disabilities. Although much is known about factors regulating RhoA activity and/or degradation, little is known about molecular mechanisms regulating RhoA expression and the subsequent effects on RhoA signaling. We hypothesized that posttranscriptional control of RhoA expression may provide a mechanism to regulate RhoA signaling and downstream effects on cell morphology. Here we uncover a cellular function for the mRNA-binding protein heterogeneous nuclear ribonucleoprotein (hnRNP) Q1 in the control of dendritic development and focal adhesion formation that involves the negative regulation of RhoA synthesis and signaling. We show that hnRNP-Q1 represses RhoA translation and knockdown of hnRNP-Q1 induced phenotypes associated with elevated RhoA protein levels and RhoA/ROCK signaling. These morphological changes were rescued by ROCK inhibition and/or RhoA knockdown. These findings further suggest that negative modulation of RhoA mRNA translation can provide control over downstream signaling and cellular morphogenesis.
authors.affiliation: Departments of Cell Biology and Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Xing
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Yao
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Williams
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Bassell
mesh_terms: D020413:3' Untranslated Regions; D000199:Actins / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D003712:Dendrites / Q000648:ultrastructure*; D022001:Focal Adhesions / Q000378:metabolism / Q000648:ultrastructure*; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D051379:Mice; D009024:Morphogenesis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D014176:Protein Biosynthesis; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D015398:Signal Transduction; D022502:Stress Fibers / Q000378:metabolism / Q000648:ultrastructure; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D000199:Actins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C486049:Syncrip protein, mouse; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein