title: X chromosome-linked intellectual disability protein PQBP1 associates with and regulates the translation of specific mRNAs.
abstract: X chromosome-linked intellectual disability is a common developmental disorder, and mutations of the polyglutamine-binding protein 1 (PQBP1) gene have been linked to this disease. In addition to existing in the nucleus as a splicing factor, PQBP1 is also found in cytoplasmic RNA granules, where it associates with RNA-binding proteins. However, the roles of cytoplasmic PQBP1 are largely unknown. Here, we show that the Drosophila homolog of PQBP1 (dPQBP1) is present in the cytoplasm of photoreceptor cells, and its loss results in defective rhabdomere morphogenesis, which is due to impaired Chaoptin translation. We also show that dPQBP1 regulates mRNA translation by interacting with dFMR1, which binds to specific mRNAs and facilitates their assembly into translating ribosomes, a function that is conserved for human PQBP1 and FMRP. Our findings reveal the conserved function of PQBP1 in mRNA translation and provide molecular insights into the pathogenic mechanisms underlying Renpenning syndrome.
authors.affiliation: Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, 2 Sipailou Rd, Nanjing, Jiangsu 210096, China and.
authors.forename: Didi
authors.initials: D
authors.lastname: Wan
authors.affiliation: Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, 2 Sipailou Rd, Nanjing, Jiangsu 210096, China and Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu 226001, China.
authors.forename: Zi Chao
authors.initials: ZC
authors.lastname: Zhang
authors.affiliation: Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, 2 Sipailou Rd, Nanjing, Jiangsu 210096, China and.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, 2 Sipailou Rd, Nanjing, Jiangsu 210096, China and.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, 2 Sipailou Rd, Nanjing, Jiangsu 210096, China and Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu 226001, China junhaihan@seu.edu.cn.
authors.forename: Junhai
authors.initials: J
authors.lastname: Han
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D041321:Chromosomes, Human, X / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics; D004331:Drosophila melanogaster; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; C119246:PQBP1 protein, human; D012333:RNA, Messenger; C055093:chp protein, Drosophila