High-resolution HIV-1 m6A epitranscriptome reveals isoform-dependent methylation clusters and unique 2-LTR transcript modifications Delphine Naquin, Sandra Blanchet, Erwin van Dijk, Lisa Bertrand, Sylvie Grégoire, et al. Nar Genomics and Bioinformatics, 2025 The N6-methyladenosine (m6A) modification of HIV-1 has been widely studied but the number and precise positions of the m6A sites remain unclear due to the lack of precision of detection methods. Using the latest Nanopore chemistry and direct m6A base-calling, we identified 18 m6A: 14 at the 3′ end and 4 in central regions of the genome. Our data reveal differential methylation of these positions between splicing isoforms. Eleven of these sites are clustered in two short segments with peak-shaped methylation profiles. Single-molecule analysis revealed that a very small number of transcripts were unmethylated in both clusters. We also identified a ∼732 nt RNA species resulting from the transcription of non-integrated viral DNA circles closed by two long terminal repeats. These transcripts started in the first LTR, terminated at the polyA site of the second LTR, and harbored six m6A sites. Five of these sites were present in other transcripts and, remarkably, had the highest methylation rates. The sixth site was methylated only in this transcript, suggesting a role for this RNA in HIV-1 infection. These findings reveal a new landscape of HIV m6A transcriptome modifications and pave the way for studies deciphering their role in the viral life cycle.
Intricate ribosome composition and translational reprogramming in epithelial-mesenchymal transition Chloé Morin, Agnès Baudin-Baillieu, Flora Nguyen Van Long, Caroline Isaac, Laure Bidou, et al. Proceedings of the National Academy of Sciences of the United States of America, 2024 Epithelial–mesenchymal transition (EMT) involves profound changes in cell morphology, driven by transcriptional and epigenetic reprogramming. However, evidence suggests that translation and ribosome composition also play key roles in establishing pathophysiological phenotypes. Using genome-wide analyses, we reported significant rearrangement of the translational landscape and machinery during EMT. Specifically, a cell line overexpressing the EMT transcription factor ZEB1 displayed alterations in translational reprogramming and fidelity. Furthermore, using riboproteomics, we unveiled an increased level of the ribosomal protein RPL36A in mesenchymal ribosomes, indicating precise tuning of ribosome composition. Remarkably, RPL36A overexpression alone was sufficient to trigger the acquisition of mesenchymal features, including a switch in the molecular pattern, cell morphology, and behavior, demonstrating its pivotal role in EMT. These findings underline the importance of translational reprogramming and fine-tuning of ribosome composition in EMT.
