Division of Neurobiology and Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Asahimachidori, Chuo-ku, Niigata, Niigata 951-8510, Japan; Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Takahisa Ogasawara
Research, Takeda Pharmaceutical Company Limited, 26-1 Muraoka-higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan
Kazumasa Yokoyama
Research, Takeda Pharmaceutical Company Limited, 26-1 Muraoka-higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan
Takako Furukawa
Division of Neurobiology and Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Asahimachidori, Chuo-ku, Niigata, Niigata 951-8510, Japan
Hiroe Hara
Research, Takeda Pharmaceutical Company Limited, 26-1 Muraoka-higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan
Kentaro Hashikami
Research, Takeda Pharmaceutical Company Limited, 26-1 Muraoka-higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan
Isamu Tsuji
Research, Takeda Pharmaceutical Company Limited, 26-1 Muraoka-higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan
Hirohide Takebayashi
Division of Neurobiology and Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Asahimachidori, Chuo-ku, Niigata, Niigata 951-8510, Japan
Shinsuke Araki
Research, Takeda Pharmaceutical Company Limited, 26-1 Muraoka-higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan
Hideyuki Okano
Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Masato Yano
Division of Neurobiology and Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Asahimachidori, Chuo-ku, Niigata, Niigata 951-8510, Japan; Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; Corresponding author
Summary: 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.
