Biomedical subjects

Yuntao Chen

Publications and source records attributed to Yuntao Chen.

3 recordsLinked to original sources

PubMed2006

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.

Animals↗

PubMed2004

Developmental abnormalities of myelin basic protein expression in fyn knock-out brain reveal a role of Fyn in posttranscriptional regulation.

Fyn protein-tyrosine kinase (PTK), a member of the Src-PTK family, is essential for myelin development in the central nervous system (CNS). The absence of Fyn activity results in defects in the morphogenesis of oligodendrocyte precursors (OPCs) and CNS hypomyelination. However, molecular mechanisms for Fyn to control CNS myelinogenesis remain elusive. Here we show that Fyn-PTK is significantly up-regulated in early OPC differentiation, concentrated in the compact myelin, and declines during myelin development. Despite the high levels of Fyn-PTK expression during early OPC differentiation, Fyn deficiency does not affect the expression of mRNAs that encode myelin structural proteins, including that for the myelin basic protein (MBP), until postnatal day 13 (P13). However, the accumulation rate of MBP mRNA is significantly attenuated during the most active period of myelinogenesis (P13 and P20). Interestingly, the absence of Fyn causes a preferential reduction of the exon-2 containing MBP mRNA isoforms derived from alternative splicing, providing the first evidence that Fyn is required for posttranscriptional regulation of MBP. Consistent with this idea, Fyn phosphorylates the selective RNA-binding protein QKI, which likely modulates the activity of QKI in binding and stabilizing the MBP mRNA. Furthermore, Fyn deficiency exerts an opposing influence on MBP isoform patterning in comparison to that by QKI deficiency. These observations collectively suggest that Fyn plays critical roles in promoting accelerated MBP expression during myelinogenesis in a MBP isoform-preferential manner, and QKI may act in the same pathway downstream of Fyn for MBP mRNA homeostasis.

Animals↗

PubMed2003

Tyrosine phosphorylation of QKI mediates developmental signals to regulate mRNA metabolism.

The selective RNA-binding protein QKI is essential for myelination in the central nervous system (CNS). QKI belongs to the family of signal transduction activators of RNA (STARs), characteristic of binding RNA and signaling molecules, therefore is postulated to regulate RNA homeostasis in response to developmental signals. Here we report that QKI acts downstream of the Src family protein tyrosine kinases (Src-PTKs) during CNS myelination. QKI selectively interacted with the mRNA encoding the myelin basic protein (MBP). Such interaction stabilized MBP mRNA and was required for the rapid accumulation of MBP mRNA during active myelinogenesis. We found that the interaction between QKI and MBP mRNA was negatively regulated by Src-PTK-dependent phosphorylation of QKI. During early myelin development, tyrosine phosphorylation of QKI in the developing myelin drastically declined, presumably leading to enhanced interactions between QKI and MBP mRNA, which was associated with the rapid accumulation of MBP mRNA and accelerated myelin production. Therefore, developmental regulation of Src-PTK-dependent tyrosine phosphorylation of QKI suggests a novel mechanism for accelerating CNS myelinogenesis via regulating mRNA metabolism.

Amino Acid Sequence↗