Essential Function, Sophisticated Regulation and Pathological Impact of the Selective RNA-Binding Protein QKI in CNS Myelin Development

Abstract

The selective RNA-binding protein QKI play a key role in advancing oligodendrocyte-dependent myelination, which is essential for the function and development of the CNS. The emerging evidence that QKI abnormalities are associated with schizophrenia and may underlie myelin impairment in this devastating disease has greatly increased interest in understanding the function of QKI. Despite the discovery of the biochemical basis for QKI–RNA interaction, a comprehensive model is currently missing regarding how QKI regulates its mRNA ligands to promote normal myelinogenesis and how deficiency of the QKI pathway is involved in the pathogenesis of human diseases that affect CNS myelin. In this review, we will focus on the role of QKI in regulating distinct mRNA targets at critical developmental steps to promote oligodendrocyte differentiation and myelin formation. In addition, we will discuss molecular mechanisms that control QKI expression and activity during normal myelinogenesis as well as the pathological impact of QKI deficiency in dysmyelination mutant animals and in human myelin disorders.

Keywords: :

• CNS myelination
• myelin disorders
• oligodendrocytes
• post-transcriptional regulation
• QKI
• RNA-binding protein
• schizophrenia

Financial & competing interests disclosure

This work is supported by NIH grant NS39551, NMSS grant RG 4010-A-2 and NASRAD Independent Investigator Award to Yue Feng. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work is supported by NIH grant NS39551, NMSS grant RG 4010-A-2 and NASRAD Independent Investigator Award to Yue Feng. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.