July 6th, 2025
Recent Publications Harnessing the Power of Translatomics
Every week we provide a digest of a small number of recent interesting papers in the field of translatomics.
In this week’s Sunday papers,
- Zhao et al. use ribosome profiling to explore the translation of circRNAs in the placenta and to uncover the potential roles the encoded proteins play in placental development and related disorders.
- Li et al. employed PEMA, a computational platform integrating bulk RNA‑seq and single‑cell RNA‑seq data from human pre‑implantation embryos, to profile metabolic gene expression patterns.
- Lin et al. developed and validated an optimized Ribo‑seq pipeline for Chlamydomonas reinhardtii.
A hidden proteome encoded by circRNAs in human placentas: Implications for uncovering preeclampsia pathogenesis
Clinical and Translational Medicine, 2024
Zhao, H., Xiong, Y., Zhou, Z., Xu, Q., Zi, Y., Zheng, X., Chen, S., Xiao, X., Gong, L., Xu, H., Liu, L et al.
Zhao et al. reveal a “hidden” proteome in the human placenta: proteins encoded by circular RNAs (circRNAs), termed circRNA‑encoded proteins (CEPs). CEPs are gaining recognition as important contributors to human health and disease, often acting as molecular decoys by interacting with shared partners of their corresponding linear-spliced RNA-encoded proteins (LEPs). Despite their emerging significance, the distribution of CEPs across human tissues and their biological functions remain poorly understood. The human placenta, known for its complex and diverse proteome essential for supporting fetal growth, provides an excellent model to investigate CEPs. This study aimed to explore the translation of circRNAs in the placenta and to uncover the potential roles these CEPs play in placental development and related disorders. Through a multi‑omics approach—RNA‑seq, ribosome profiling, and LC‑MS/MS—in placentas from all trimesters, they identified 528 circRNAs with evidence of ribosomal engagement and 139 translated into proteins. These CEPs are smaller, more stable, more hydrophobic, and share strong structural homology with their linear protein counterparts (LEPs), suggesting they act as “bait” to modulate LEP function.
Notably, the authors focused on circPRKCB119aa, a CEP derived from circPRKCB, and demonstrated its pathophysiological relevance in preeclampsia. Through qRT‑PCR, Western blot, immunofluorescence, and functional assays, they showed that circPRKCB119aa enhances trophoblast autophagy by inhibiting phosphorylation of its cognate protein kinase C β (PKCβ), thereby promoting cell migration, invasion, and vascular remodeling—processes disrupted in preeclampsia. Overall, this study establishes a systematic atlas of placental CEPs, supports the “protein bait” mechanism, and links CEP function to placental development and disease. The work introduces the Placental Microprotein Bank, offering a valuable resource for future exploration of placental biology and preeclampsia treatment strategies.
Learn more about EIRNA Bio’s ribosome profiling service here.
Pre-implantation embryo metabolism identified by PEMA reveals endogenous lactate insufficiency contributes to pre-implantation development arrest
Fundamental Research, 2024
Li, J., Hou, W., Zhao, Q., Xi, H., Liu, W., Xiao, S., Song, E., Zhu, L., Cai, Y., Zong, M., Zhang, J et al.
Pre‑implantation embryo arrest remains a major barrier in assisted reproduction, often linked to metabolic insufficiencies. Lactate, produced via glycolysis, has been suggested as a crucial energy source during early embryo development, but its functional contribution in human embryos has not been definitively demonstrated. Li et al. employed PEMA, a computational platform integrating bulk RNA‑seq and single‑cell RNA‑seq data from human pre‑implantation embryos—both normal 8‑cell stage and developmentally arrested (PIDA) embryos—to profile metabolic gene expression patterns. Bulk RNA‑seq provided global transcriptome context, while single‑cell RNA‑seq revealed cell‑level heterogeneity across blastomeres.
Both transcriptomic approaches revealed a deficiency in lactate dehydrogenase A (LDHA) expression in arrested embryos compared to normally developing ones. PEMA predicted reduced intracellular lactate production in PIDA embryos. This prediction was validated experimentally by measuring metabolic intermediates. Supplementing culture media with exogenous lactate partially restored developmental progression in arrested embryos, raising the blastocyst formation rate. By integrating RNA‑seq modalities with advanced modeling, the study identifies endogenous lactate insufficiency as a key metabolic bottleneck contributing to pre‑implantation developmental arrest. The beneficial effect of lactate supplementation suggests a promising avenue for improving embryo culture conditions. This work underscores the power of combining bulk and single‑cell transcriptomics to map metabolic landscapes and offers practical strategies to advance reproductive technology.
Learn more about EIRNA Bio’s ribosome profiling service here.
Optimised Ribosome Profiling Reveals New Insights Into Translational Regulation in Synchronised Chlamydomonas reinhardtii Cultures
Plant, Cell & Environment, 2025
Lin, Y.L., Kuo, E.Y., Wang, S.Y., Lee, C.C. and Fang, S.C.
Ribosome profiling (Ribo‑seq) offers a high-resolution, global snapshot of mRNA translation. While it has been applied in Chlamydomonas, previous datasets have had limitations in mapping accuracy and frame specificity. Lin et al. developed and validated an optimized Ribo‑seq pipeline for Chlamydomonas reinhardtii. Their protocol improved ribosome-protected fragment (RPF) mapping to coding sequences, reduced bias, and achieved strong 3‑nucleotide periodicity—enhancing data quality over prior efforts. They also refined rRNA removal and polysome extraction buffers, achieving >94 % mapping to main open reading frames and reliable P-site localization.
By pairing Ribo‑seq with RNA‑seq from synchronized cultures at G1 (light) and early S/M (synthesis/mitosis, dark) stages, they detected ~1,688 differentially translated genes after accounting for transcript levels. Notably, many core cell-cycle and DNA replication genes showed upregulated translation at S/M, indicating translational control plays a pivotal role in cell-cycle progression. Enhanced periodicity allowed identification of numerous uORFs, some exhibiting diurnal regulation patterns. These may represent novel translational control elements influencing gene expression timing. Lin et al. provide a robust Ribo‑seq resource linked to the Chlamydomonas genome, improving annotation and offering valuable data for translational regulation research. Their findings underscore the importance of translation-level regulation in cell-cycle control and suggest uORFs as potential regulatory nodes—advancing both method and biological insight in algal genomics.
Learn more about EIRNA Bio’s ribosome profiling services here.