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: Didi Wan, Zi Chao Zhang, Xiaoyan Zhang, Qian Li, Junhai Han
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 24 Issue 16 Pg. 4599-614 (Aug 15 2015) ISSN: 1460-2083 [Electronic] England
• PMID: 26002102 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Carrier Proteins
• DNA-Binding Proteins
• Drosophila Proteins
• Membrane Glycoproteins
• Nuclear Proteins
• PQBP1 protein, human
• RNA, Messenger
• chp protein, Drosophila

Topics

• Animals
• Carrier Proteins (genetics, metabolism)
• Chromosomes, Human, X (genetics, metabolism)
• DNA-Binding Proteins
• Drosophila Proteins (biosynthesis, genetics)
• Drosophila melanogaster
• Genetic Diseases, X-Linked (genetics, metabolism)
• Humans
• Intellectual Disability (genetics, metabolism)
• Membrane Glycoproteins (biosynthesis, genetics)
• Nuclear Proteins (genetics, metabolism)
• Protein Biosynthesis
• RNA, Messenger (genetics, metabolism)