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However, their prevalence across human tissues and biological roles remain largely unexplored. The placenta is an ideal model for identifying CEPs due to its considerable protein diversity that is required to sustain fetal development during pregnancy. The aim of this study was to evaluate circRNA translation in the human placenta, and the potential roles of the CEPs in placental development and dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Multiomics approaches, including RNA sequencing, ribosome profiling, and LC\u2010MS\/MS analysis, were utilised to identify novel translational events of circRNAs in human placentas. Bioinformatics methods and the protein bait hypothesis were employed to evaluate the roles of these newly discovered CEPs in placentation and associated disorders. The pathogenic role of a recently identified CEP circPRKCB119aa in preeclampsia was investigated through qRT\u2010PCR, Western blotting, immunofluorescence imaging and phenotypic analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that 528 placental circRNAs bound to ribosomes with active translational elongation, and 139 were translated to proteins. The CEPs showed considerable structural homology with their cognate LEPs, but are more stable, hydrophobic and have a lower molecular\u2010weight than the latter, all of which are conducive to their function as baits. On this basis, CEPs are deduced to be closely involved in placental function. Furthermore, we focused on a novel CEP circPRKCB119aa, and illuminated its pathogenic role in preeclampsia; it enhanced trophoblast autophagy by acting as a bait to inhibit phosphorylation of the cognate linear isoform PKC\u03b2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We discovered a hidden circRNA\u2010encoded proteome in the human placenta, which offers new insights into the mechanisms underlying placental development, as well as placental disorders such as preeclampsia.<\/jats:p><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>A hidden circRNA\u2010encoded proteome in the human placenta was extensively identified and systematically characterised.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The circRNA\u2010encoded proteins (CEPs) are potentially related to placental development and associated disorders.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>A novel conserved CEP circPRKCB119aa enhanced trophoblast autophagy by inhibiting phosphorylation of its cognate linear\u2010spliced isoform protein kinase C (PKC) \u03b2 in preeclampsia.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><\/jats:sec>","DOI":"10.1002\/ctm2.1759","type":"journal-article","created":{"date-parts":[[2024,7,13]],"date-time":"2024-07-13T03:54:36Z","timestamp":1720842876000},"source":"Crossref","is-referenced-by-count":1,"title":["A hidden proteome encoded by circRNAs in human placentas: Implications for uncovering preeclampsia pathogenesis"],"prefix":"10.1002","volume":"14","author":[{"given":"Huanqiang","family":"Zhao","sequence":"first","affiliation":[{"name":"The Shanghai Key Laboratory of Female Reproductive Endocrine\u2010Related Diseases Obstetrics and Gynecology Hospital, Fudan University  Shanghai China"},{"name":"Institute of Maternal and Child Medicine Shenzhen Maternity and Child Healthcare Hospital  Shenzhen Guangdong Province 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