Chemical RNA Modifications: The Plant Epitranscriptome

International audienceRNA post-transcriptional modifications create an additional layer to control mRNA transcription, fate, and expression. Considering that they are non-genetically encoded, can be of reversible nature, and involved in fine-tuning gene expression, the landscape of RNA modifications has been coined the "RNA epig-enome" or "epitranscriptome." Our knowledge of the plant epitranscriptome is so far limited to 3′-uridylation and internal m 6 A and m 5 C modifications in Arabidopsis. m 6 A is the most abundant and well-studied modification on mRNAs, and involves the activities of evolutionarily conserved "writer" (methyltransfer-ase), "reader" (RNA binding proteins), and "eraser" (demethylases) proteins. In Arabidopsis, m 6 A is crucial for embryogenesis, post-embryonic growth, development , phase transition, and defense responses. Conversely to animals, our understanding of the roles of m 6 A is limited to the finding that it is an mRNA stabilizing mark. Yet likely to exist, its roles in controlling plant mRNA maturation, trafficking , storage, and translation remain unexplored. The m 5 C mark is much less abundant on the transcriptome and our knowledge in plants is more limited. Nonetheless, it is also an important epitranscriptomic mark involved in plant development and adaptive response. Here, we explore the current information on m 6 A and m 5 C marks and report knowledge on their distribution, features, and molecular, cellular , and physiological roles, therefore, uncovering the fundamental importance in plant development and acclimation of RNA epigenetics. Likely to be widespread in the green lineage and given their crucial roles in eukaryotes, the fostering of data and knowledge of epitranscriptome from cultivated plant species is of the utmost importance

An RNA toolbox for cancer immunotherapy

Cancer immunotherapy has revolutionized oncology practice. However, current protein and cell therapy tools used in cancer immunotherapy are far from perfect, and there is room for improvement regarding their efficacy and safety. RNA-based structures have diverse functions, ranging from gene expression and gene regulation to pro-inflammatory effects and the ability to specifically bind different molecules. These functions make them versatile tools that may advance cancer vaccines and immunomodulation, surpassing existing approaches. These technologies should not be considered as competitors of current immunotherapies but as partners in synergistic combinations and as a clear opportunity to reach more efficient and personalized results. RNA and RNA derivatives can be exploited therapeutically as a platform to encode protein sequences, provide innate pro-inflammatory signals to the immune system (such as those denoting viral infection), control the expression of other RNAs (including key immunosuppressive factors) post-transcriptionally and conform structural scaffoldings binding proteins that control immune cells by modifying their function. Nascent RNA immunotherapeutics include RNA vaccines encoding cancer neoantigens, mRNAs encoding immunomodulatory factors, viral RNA analogues, interference RNAs and protein-binding RNA aptamers. These approaches are already in early clinical development with promising safety and efficacy results