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Lu J, Cheng C, Cheng ZC, et al. The dual role of RFX6 in directing β cell development and insulin production. J Mol Endocrinol. 2021;66(2):129-140doi: 10.1530/JME-20-0119.
Lu, J., Cheng, C., Cheng, Z. C., Wu, Q., Shen, H., Yuan, M. X., Zhang, B., & Yang, J. K. (2021). The dual role of RFX6 in directing β cell development and insulin production. Journal of molecular endocrinology, 66(2), 129-140. https://doi.org/10.1530/JME-20-0119
Lu, Jing, et al. "The dual role of RFX6 in directing β cell development and insulin production." Journal of molecular endocrinology vol. 66,2 (2021): 129-140. doi: https://doi.org/10.1530/JME-20-0119
Lu J, Cheng C, Cheng ZC, Wu Q, Shen H, Yuan MX, Zhang B, Yang JK. The dual role of RFX6 in directing β cell development and insulin production. J Mol Endocrinol. 2021 Feb;66(2):129-140. doi: 10.1530/JME-20-0119. PMID: 33350979.
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J Mol Endocrinol. 2021 Feb;66(2):129-140. doi: 10.1530/JME-20-0119.

The dual role of RFX6 in directing β cell development and insulin production.

Journal of molecular endocrinology

Jing Lu, Cheng Cheng, Zhen-Chao Cheng, Qian Wu, Han Shen, Ming-Xia Yuan, Bo Zhang, Jin-Kui Yang

Affiliations

  1. Beijing Key Laboratory of Diabetes Research and Care, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
  2. Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing, China.
  3. BeiJing School, Beijing, China.
  4. HangZhou XueJun High School, Hangzhou, China.

PMID: 33350979 DOI: 10.1530/JME-20-0119

Abstract

RFX6 transcription factor is believed to play a central role in directing cell development of insulin-producing pancreatic islet. RFX6 homozygous mutations cause syndromic neonatal diabetes with hypoplastic pancreas. However, RFX6 heterozygous mutations cause maturity-onset diabetes of the young (MODY) with normal pancreas development. Here, we show that RFX6 may control islet cell development and insulin production in different manners. The rfx6 knockout zebrafish generated by CRISPR/Cas9 exhibited an overt diabetes phenotype. Pancreatic islet failed to form compact structures in the knockout fish. While endocrine pancreatic islet non-β-cells were absent, insulin-producing β-cells were present in the knockout fish. Although insulin mRNA level was normal in the β-cells of the knockout fish, insulin protein level was decreased. High-throughput RNA sequencing (RNAseq) showed that differentially expressed genes were enriched in the translation term in islet β-cells from the knockout fish. Chromatin immunoprecipitation sequencing (ChIPseq) of normally developed islet β-cells from mice demonstrated that rfx6 interacted with translation initiation factors and controlled insulin translation. Our data indicate that Rfx6 may act as a transcription factor regulating the transcription of genes involved in mRNA translation, which may represent a new mechanism and treatment strategy for diseases.

Keywords: Cas9; ChIP-seq; RNA-seq; Rfx6; insulin; islet development

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