title: Retracted: Overexpression of αCP2, a translational repressor of GAP-43, inhibited axon outgrowth during development in Xenopus laevis.
abstract: The 3'-untranslated regions (3'-UTRs) of growth-associated protein 43 (GAP-43), which is crucial for neural development and axonal regeneration, are highly conserved among vertebrates. Previous studies in mammals have identified one U-rich cis element within GAP-43 3'-UTR and several trans factors that regulate its mRNA stability. However, much less is known in lower vertebrates. The Xenopus GAP-43 3'-UTR, despite its high similarity with those in higher vertebrates, contains unique CU-rich sequences, suggesting the existence of novel cis elements and trans factors. In current study, we isolated four proteins bound to GAP-43 3'-UTR from juvenile frog brain using affinity purification. Mass spectrometry identified Hu antigen D (HuD) and poly(C) binding protein 2 (αCP2) as the proteins forming 48- and 44-kDa ribonucleoprotein complexes, respectively. We validated the association between αCP2 and GAP-43 3'-UTR in vivo. After confirming the post-transcriptional effects of αCP2 on GAP-43 expression, we demonstrated that αCP2 directly inhibited the translation of GAP-43 gene, without affecting its mRNA stability. αCP2 overexpression led to decreased level of GAP-43 protein and significantly inhibited axonal outgrowth in primarily cultured neurons. Our study therefore provided insights on novel functions of αCP2 in vertebrate nervous system during development and new mechanisms of post-transcriptional regulation for GAP-43 gene.
authors.affiliation: Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Shenggang
authors.initials: S
authors.lastname: Sun
authors.forename: Xuebing
authors.initials: X
authors.lastname: Cao
authors.forename: Xuejun
authors.initials: X
authors.lastname: Deng
authors.forename: Yunjian
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhu
mesh_terms: D020413:3' Untranslated Regions; D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002478:Cells, Cultured; D019922:GAP-43 Protein / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D014176:Protein Biosynthesis / Q000235:genetics*; D020871:RNA Stability; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D019922:GAP-43 Protein; D012097:Repressor Proteins