title: Transport and translation of MBP mRNA is regulated differently by distinct hnRNP proteins.
abstract: In the developing nervous system, abundant synthesis of myelin basic protein (MBP) in oligodendrocytes is required for the formation of compact myelin sheaths around axons. The MBP mRNA is known to be transported into the processes of oligodendrocytes. However, knowledge of the regulatory mechanisms that ensure the tight temporal and spatial control of MBP translation within these processes is limited. Here, we have identified novel regions within the 3'-UTR of the MBP mRNA that are responsible for the regulation of its translation, and we have demonstrated that each of the mRNA-binding proteins heterogeneous nuclear ribonucleoprotein (hnRNP)-A2, hnRNP-K and hnRNP-E1 serve distinct functions to regulate controlled and localized protein synthesis. hnRNP-A2 is responsible for mRNA transport, not for translational inhibition. By contrast, hnRNP-K and hnRNP-E1 play opposing roles in the translational regulation of MBP mRNA. We have identified shared binding sites within the 3'-UTR, and show that translation is promoted by the exchange of inhibitory hnRNP-E1 for stimulatory hnRNP-K. We further show that this molecular switch in the MBP messenger RNA-ribonucleoprotein (mRNP) complex, which regulates the synthesis of MBP, is important for the normal growth and extension of myelin sheets.
authors: Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus C, Denmark.
authors: Julie
authors: J
authors: Torvund-Jensen
authors: Jes
authors: J
authors: Steengaard
authors: Lasse
authors: L
authors: Reimer
authors: Linda B
authors: LB
authors: Fihl
authors: Lisbeth S
authors: LS
authors: Laursen
mesh_terms: D001692:Biological Transport; D057809:HEK293 Cells; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics / Q000378:metabolism*; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D004676:Myelin Basic Protein / Q000235:genetics* / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D004676:Myelin Basic Protein
keywords: Cellular asymmetry; Local translation; Myelin basic protein; Oligodendrocyte; RNA-binding proteins