Title |
Rescuing qkv Dysmyelination by a Single Isoform of the Selective RNA-Binding Protein QKI
|
---|---|
Published in |
Journal of Neuroscience, November 2006
|
DOI | 10.1523/jneurosci.2677-06.2006 |
Pubmed ID | |
Authors |
Lixia Zhao, Donghua Tian, Mingjing Xia, Wendy B. Macklin, Yue Feng |
Abstract |
Alternative splicing of the qkI transcript generates multiple isoforms of the selective RNA-binding protein QKI, which play key roles in controlling the homeostasis of their mRNA targets. QKI deficiency in oligodendrocytes of homozygous quakingviable (qkV/qkV) mutant mice results in severe hypomyelination, indicating the essential function of QKI in myelinogenesis. However, the molecular mechanisms by which QKI controls myelination remain elusive. We report here that QKI-6 is the most abundant isoform in brain and is preferentially reduced in the qkV/qkV mutant during normal myelinogenesis. To test whether QKI-6 is the predominant isoform responsible for advancing CNS myelination, we developed transgenic mice that express Flag-QKI-6 specifically in the oligodendroglia lineage, driven by the proteolipid protein (PLP) promoter. When introduced into the qkV/qkV mutant, the QKI-6 transgene rescues the severe tremor and hypomyelination phenotype. Electron microscopic studies further revealed that the Flag-QKI-6 transgene is sufficient for restoring compact myelin formation with normal lamellar periodicity and thickness. Interestingly, Flag-QKI-6 preferentially associates with the mRNA encoding the myelin basic protein (MBP) and rescues MBP expression from the beginning of myelinogenesis. In contrast, Flag-QKI-6 binds the PLP mRNA with lower efficiency and has a minimal impact on PLP expression until much later, when the expression level of QKI-6 in the transgenic animal significantly exceeds what is needed for normal myelination. Together, our results demonstrate that QKI-6 is the major isoform responsible for CNS myelination, which preferentially promotes MBP expression in oligodendrocytes. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 5% |
Unknown | 18 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 4 | 21% |
Student > Doctoral Student | 4 | 21% |
Other | 3 | 16% |
Student > Ph. D. Student | 3 | 16% |
Student > Bachelor | 1 | 5% |
Other | 4 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 8 | 42% |
Medicine and Dentistry | 4 | 21% |
Neuroscience | 3 | 16% |
Biochemistry, Genetics and Molecular Biology | 3 | 16% |
Unknown | 1 | 5% |