QKI binds MAP1B mRNA and enhances MAP1B expression during oligodendrocyte development.
Microtubule-associated protein 1B (MAP1B) is essential for neural development. Besides the abundant expression in neurons, MAP1B recently was found in myelinating oligodendroglia. Moreover, MAP1B deficiency causes delayed myelin development, suggesting the functional importance of MAP1B in oligodendroglia. However, molecular mechanisms that control MAP1B expression in oligodendroglia remain elusive. We report here that MAP1B mRNA is markedly up-regulated in the oligodendroglia cell line CG4 upon induced differentiation, leading to elevated MAP1B protein production. A coordinated regulation of homeoprotein transcription factors was observed during CG4 cell differentiation, which recapitulates the regulation in neurons that promotes MAP1B transcription. Hence, transcriptional regulation of MAP1B appears to be a common mechanism in both neurons and oligodendroglia. In addition, we found posttranscriptional regulation of MAP1B mRNA by the selective RNA-binding protein QKI in oligodendroglia. The 3'UTR of MAP1B mRNA interacts with QKI, and oligodendroglia-specific QKI-deficiency in the quakingviable mutant mice resulted in reduced MAP1B mRNA expression. Moreover, RNAi-mediated QKI-knockdown caused destabilization of the MAP1B mRNA in CG4 cells. Furthermore, forced expression of exogenous QKI was sufficient for promoting MAP1B expression. Because QKI is absent in neurons, QKI-dependent stabilization of MAP1B mRNA provides a novel mechanism for advancing MAP1B expression specifically in oligodendroglia during brain development.
Zhao
Lixia
L
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Ku
Li
L
Chen
Yuntao
Y
Xia
Mingjing
M
LoPresti
Patrizia
P
Feng
Yue
Y
D000818:Animals; D001933:Brain Stem / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D018398:Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D008821:Mice, Quaking; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism*; D034622:RNA Interference; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
D018398:Homeodomain Proteins; D008869:Microtubule-Associated Proteins; C098217:Qk protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C085284:microtubule-associated protein 1B