PT  - JOURNAL ARTICLE
AU  - Torvund-Jensen, Julie
AU  - Steengaard, Jes
AU  - Reimer, Lasse
AU  - Fihl, Linda B.
AU  - Laursen, Lisbeth S.
TI  - Transport and translation of MBP mRNA is regulated differently by distinct hnRNP proteins
AID  - 10.1242/jcs.140855
DP  - 2014 Apr 01
TA  - Journal of Cell Science
PG  - 1550--1564
VI  - 127
IP  - 7
4099  - http://jcs.biologists.org/content/127/7/1550.short
4100  - http://jcs.biologists.org/content/127/7/1550.full
SO  - J. Cell Sci.2014 Apr 01; 127
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.