RT Journal Article
SR Electronic
T1 Transport and translation of MBP mRNA is regulated differently by distinct hnRNP proteins
JF Journal of Cell Science
JO J. Cell Sci.
FD The Company of Biologists Ltd
SP 1550
OP 1564
DO 10.1242/jcs.140855
VO 127
IS 7
A1 Torvund-Jensen, Julie
A1 Steengaard, Jes
A1 Reimer, Lasse
A1 Fihl, Linda B.
A1 Laursen, Lisbeth S.
YR 2014
UL http://jcs.biologists.org/content/127/7/1550.abstract
AB 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.