Rbp9 is a Drosophila RNA-binding protein that shares a high level of sequence similarity with Drosophila elav and human Hu proteins. Loss of function alleles of elav are embryonic lethal causing abnormal central nervous system (CNS) development, and Hu is implicated in the development of paraneoplastic neurological syndrome associated with small cell lung cancer. To elucidate the role of Rbp9, we generated Rbp9 mutant flies and examined them for symptoms related to paraneoplastic encephalomyelitis. Although Rbp9 proteins begin to appear from the middle of the pupal period in the cortex of the CNS, the Rbp9 mutants showed no apparent defects in development. However, as the mutant adult flies grew older, they showed reduced locomotor activities and lived only one-half of the life expectancy of wild-type flies. To understand the molecular mechanism underlying this symptom, gene expression profiles in Rbp9 mutants were analyzed and potential target genes were further characterized. Reduced expression of cell adhesion molecules was detected, and defects in the blood-brain barrier (BBB) of Rbp9 mutant brains could be seen. Putative Rbp9-binding sites were found in introns of genes that function in cell adhesion. Therefore, Rbp9 may regulate the splicing of cell adhesion molecules, critical for the formation of the BBB.
Bibliographical noteFunding Information:
This work was supported by grant M10412000086-04N1200-08610 from the Korea Ministry of Science and Technology and R01-2006-000-10783 from the Korea Science and Engineering Foundation to J.K.-H.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology