The RNA-binding protein MARF1 promotes cortical neurogenesis through its RNase activity domain

• Published in: Scientific reports 2017-04, Vol.7 (1), p.1155-11, Article 1155
• Main Authors: Kanemitsu, Yoshitaka, Fujitani, Masashi, Fujita, Yuki, Zhang, Suxiang, Su, You-Qiang, Kawahara, Yukio, Yamashita, Toshihide
• Format: Article
• Language: English
• Subjects: 13/51; 13/89; 38/1; 42; 42/89; 631/136/368/2430; 631/378/2571/2579; 64; 64/60; Animals; Cell Cycle Proteins - metabolism; Cell Differentiation; Cells, Cultured; Cerebral Cortex - embryology; Clonal deletion; Deletion mutant; Electroporation; Embryogenesis; Gene Expression Profiling; Gene regulation; Humanities and Social Sciences; Meiosis; Mice, Inbred ICR; multidisciplinary; Neural stem cells; Neurogenesis; Pluripotent Stem Cells - physiology; Post-transcription; Ribonuclease; Ribonucleases - metabolism; Ribonucleic acid; RNA; RNA-binding protein; RNA-Binding Proteins - metabolism; Science; Science (multidisciplinary); Transcription factors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-01317-y

Cortical neurogenesis is a fundamental process of brain development that is spatiotemporally regulated by both intrinsic and extrinsic cues. Although recent evidence has highlighted the significance of transcription factors in cortical neurogenesis, little is known regarding the role of RNA-binding proteins (RBPs) in the post-transcriptional regulation of cortical neurogenesis. Here, we report that meiosis arrest female 1 (MARF1) is an RBP that is expressed during neuronal differentiation. Cortical neurons expressed the somatic form of MARF1 (sMARF1) but not the oocyte form (oMARF1). sMARF1 was enriched in embryonic brains, and its expression level decreased as brain development progressed. Overexpression of sMARF1 in E12.5 neuronal progenitor cells promoted neuronal differentiation, whereas sMARF1 knockdown decreased neuronal progenitor differentiation in vitro . We also examined the function of sMARF1 in vivo using an in utero electroporation technique. Overexpression of sMARF1 increased neuronal differentiation, whereas knockdown of sMARF1 inhibited differentiation in vivo . Moreover, using an RNase domain deletion mutant of sMARF1, we showed that the RNase domain is required for the effects of sMARF1 on cortical neurogenesis in vitro . Our results further elucidate the mechanisms of post-transcriptional regulation of cortical neurogenesis by RBPs.