The selective RNA-binding protein quaking I (QKI) is necessary and sufficient for promoting oligodendroglia differentiation

被引:50
作者
Chen, Yuntao
Tian, Donghua
Ku, Li
Osterhout, Donna J.
Feng, Yue
机构
[1] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA
[2] SUNY Upstate Med Univ, Dept Cell & Dev Biol, Syracuse, NY 13210 USA
关键词
D O I
10.1074/jbc.M702045200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Quaking I ( QKI) is a selective RNA-binding protein essential for myelination of the central nervous system. Three QKI isoforms with distinct C termini and subcellular localization, namely QKI-5, QKI-6, and QKI-7, are expressed in oligodendroglia progenitor cells (OPCs) prior to the initiation of myelin formation and implicated in promoting oligodendrocyte lineage development. However, the functional requirement for each QKI isoform and the mechanisms by which QKI isoforms govern OPC development still remain elusive. We report here that exogenous expression of each QKI isoform is sufficient to enhance differentiation of OPCs with different efficiency, which is abolished by a point mutation that abrogates the RNA binding activity of QKI. Reciprocally, small interfering RNA-mediated QKI knockdown blocks OPC differentiation, which can be partly rescued by QKI-5 and QKI-6 but not by QKI-7, indicating the differential requirement of QKI isoform function in advancing OPC differentiation. Furthermore, we found that abrogation of OPC differentiation, as a result of QKI deficiency, is not due to altered proliferation capacity or cell cycle progression. These results indicate that QKI isoforms are necessary and sufficient for promoting OPC development, which must involve direct influence of QKI on differentiation/ maturation of OPCs independent of cell cycle exit, likely via regulating the expression of the target mRNAs of QKI that support OPC differentiation.
引用
收藏
页码:23553 / 23560
页数:8
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