Sbp2l contributes to oligodendrocyte maturation through translational control in Tcf7l2 signaling

Masato Yugami; Yoshika Hayakawa-Yano; Takahisa Ogasawara; Kazumasa Yokoyama; Takako Furukawa; Hiroe Hara; Kentaro Hashikami; Isamu Tsuji; Hirohide Takebayashi; Shinsuke Araki; Hideyuki Okano; Masato Yano

doi:10.1016/j.isci.2023.108451

Sbp2l contributes to oligodendrocyte maturation through translational control in Tcf7l2 signaling

iScience. 2023 Nov 16;26(12):108451. doi: 10.1016/j.isci.2023.108451. eCollection 2023 Dec 15.

Authors

Affiliations

¹ Research, Takeda Pharmaceutical Company Limited, 26-1 Muraoka-higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.
² Division of Neurobiology and Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Asahimachidori, Chuo-ku, Niigata, Niigata 951-8510, Japan.
³ Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

Abstract

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.

Keywords: Biochemistry; Biological sciences; Cell biology.