Sbp2l contributes to oligodendrocyte maturation through translational control in Tcf7l2 signaling

オリゴデンドロサイト特異的に発現するRNA結合蛋白質のスクリーニングを行い、RNA結合蛋白質Sbp2Lを同定しました。さらにSbp2Lがオリゴデンドロサイトの成熟に寄与するTcf7l2を介した分子経路を明らかにしました。RNA結合ドメイン以外の領域が天然変性スコアの極めて高い分子です。

Oligodendrocytes (OLs) are the myelin-forming cells in the CNS that support neurons through the insulating sheath of axons. This unique feature and developmental processes are achieved by extrinsic and intrinsic gene expression programs, where RNA-binding proteins can contribute to dynamic and fine-tuned post-transcriptional regulation. Here, we identified SECIS-binding protein 2-like (Sbp2l), which is specifically expressed in OLs by integrated transcriptomics. Histological analysis revealed that Sbp2l is a molecular marker of OL maturation. Sbp2l knockdown (KD) led to suppression of matured OL markers, but not a typical selenoprotein, Gpx4. Transcriptome analysis demonstrated that Sbp2l KD decreased cholesterol-biosynthesis-related genes regulated by Tcf7l2 transcription factor. Indeed, we confirmed the downregulation of Tcf7l2 protein without changing its mRNA in Sbp2l KD OPCs. Furthermore, Sbp2l KO mice showed the decrease of Tcf7l2 protein and deficiency of OL maturation. These results suggest that Sbp2l contributes to OL maturation by translational control of Tcf7l2.

Authors: Masato Yugami, Yoshika Hayakawa-Yano, Takahisa Ogasawara, Kazumasa Yokoyama, Takako Furukawa, Hiroe Hara, Kentaro Hashigami, Isamu Tsuji, Hirohide Takebayashi, Shinsuke Araki, Hideyuki Okano and Masato Yano

Journal:iScience 26(12), 108451

DOI: https://doi.org/10.1016/j.isci.2023.108451