2026-08-28 ジョージア工科大学
Scientific rendering of multiple DNA double helices with several embedded ribonucleotides highlighted in red along the strands.
＜関連情報＞
- https://news.research.gatech.edu/2026/08/28/georgia-tech-researchers-discover-new-layer-human-genome
- https://www.cell.com/cell/abstract/S0092-8674(26)00922-0
ヒト核リボゲノムは、DNAに埋め込まれたリボヌクレオチドが転写関連DNAスーパーコイルのエピジェネティックな調節因子であることを示している Human nuclear ribomes reveal DNA-embedded ribonucleotides as epigenetic modulators of transcription-associated DNA supercoiling
Deepali L. Kundnani ∙ Yeunsoo Lee ∙ Taehwan Yang ∙ … ∙ Soojin V. Yi ∙ Nataša Jonoska ∙ Francesca Storici
Cell Published:August 28, 2026
DOI:https://doi.org/10.1016/j.cell.2026.07.053
Highlights
- Human ribomes reveal ∼1 million DNA-embedded rNMPs per nuclear genome
- rNMPs accumulate at transcription start sites, CpG islands, R-loops, and G4s
- RNase H2 loss reveals Top1-modulated rG enrichment at TSSs associated with transcription
- Embedded rNMPs function as epigenetic modulators of DNA supercoiling
Summary
Ribonucleoside monophosphates (rNMPs) are the most abundant non-canonical nucleotides in DNA, yet their distribution and function in the human nuclear genome remain unclear. We present high-resolution maps of ∼1 million rNMPs per genome across diverse human cells, revealing a non-random nuclear “ribome,” the genome-wide landscape of embedded rNMPs, enriched in GC-rich regions, regulatory elements, and telomeres. Ribonucleotide-enriched zones (REZs) cluster near transcription start sites (TSSs), coincide with C–phosphate–G (CpG) islands, R-loops, and G4 structures, and scale with gene expression. Ribonuclease (RNase) H2 deficiency increases rGMP levels and is associated with topoisomerase 1 (Top1)-dependent, strand-biased rNMP enrichment near TSSs, while Top1 depletion further enhances rGMP accumulation. RNase H2-mediated nicking at rNMPs alters DNA supercoiling in vitro, and RNH2A-deficient cells show altered supercoiling at rNMP-enriched TSSs. Our findings identify embedded rNMPs as epigenetic modulators of DNA supercoiling linked to DNA sequence and transcription, revealing a connection between ribonucleotide processing and transcription-associated DNA topology in human cells.
