title: The RNA-binding protein human antigen R controls global changes in gene expression during Schwann cell development.
abstract: An important prerequisite to myelination in peripheral nerves is the establishment of one-to-one relationships between axons and Schwann cells. This patterning event depends on immature Schwann cell proliferation, apoptosis, and morphogenesis, which are governed by coordinated changes in gene expression. Here, we found that the RNA-binding protein human antigen R (HuR) was highly expressed in immature Schwann cells, where genome-wide identification of its target mRNAs in vivo in mouse sciatic nerves using ribonomics showed an enrichment of functionally related genes regulating these processes. HuR coordinately regulated expression of several genes to promote proliferation, apoptosis, and morphogenesis in rat Schwann cells, in response to NRG1, TGFβ, and laminins, three major signals implicated in this patterning event. Strikingly, HuR also binds to several mRNAs encoding myelination-related proteins but, contrary to its typical function, negatively regulated their expression, likely to prevent ectopic myelination during development. These functions of HuR correlated with its abundance and subcellular localization, which were regulated by different signals in Schwann cells.
authors.affiliation: CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, 48160 Derio, Bizkaia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Iruarrizaga-Lejarreta
authors.forename: Marta
authors.initials: M
authors.lastname: Varela-Rey
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Lozano
authors.forename: David
authors.initials: D
authors.lastname: Fernández-Ramos
authors.forename: Naiara
authors.initials: N
authors.lastname: Rodríguez-Ezpeleta
authors.forename: Nieves
authors.initials: N
authors.lastname: Embade
authors.forename: Shelly C
authors.initials: SC
authors.lastname: Lu
authors.forename: Peter M
authors.initials: PM
authors.lastname: van der Kraan
authors.forename: Esmeralda N
authors.initials: EN
authors.lastname: Blaney Davidson
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
authors.forename: Rhona
authors.initials: R
authors.lastname: Mirsky
authors.forename: Kristján R
authors.initials: KR
authors.lastname: Jessen
authors.forename: Ana María
authors.initials: AM
authors.lastname: Aransay
authors.forename: José M
authors.initials: JM
authors.lastname: Mato
authors.forename: María L
authors.initials: ML
authors.lastname: Martínez-Chantar
authors.forename: Ashwin
authors.initials: A
authors.lastname: Woodhoo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D051959:ELAV Proteins / Q000096:biosynthesis / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000166:cytology* / Q000502:physiology*
chemical_list: D051959:ELAV Proteins; D016601:RNA-Binding Proteins