2025-05-05 イェール大学
<関連情報>
- https://news.yale.edu/2025/05/05/yale-developed-method-offers-view-earliest-stages-rna-production
- https://www.cell.com/molecular-cell/abstract/S1097-2765(25)00187-X
新生RNAの迅速なフォールディングが真核生物のRNA生合成を制御する Rapid folding of nascent RNA regulates eukaryotic RNA biogenesis
Leonard Schärfen ∙ Isaac W. Vock ∙ Matthew D. Simon ∙ Karla M. Neugebauer
Molecular Cell Published:March 25, 2025
DOI:https://doi.org/10.1016/j.molcel.2025.02.025
Graphical abstract
Highlights
- CoSTseq detects nascent RNA base pairing upon exit from RNA polymerases in vivo
- Base pairing occurs rapidly within 25 bp of transcription after addition to the RNA
- Nascent rRNA structure is vastly different from mature rRNA
- Cytoplasmic mRNA structure is largely indistinguishable from nascent pre-mRNA
Summary
RNA’s catalytic, regulatory, or coding potential depends on structure formation. Because base pairing occurs during transcription, early structural states can govern RNA processing events and dictate the formation of functional conformations. These co-transcriptional states remain mostly unknown. Here, we develop co-transcriptional structure tracking (CoSTseq), which detects nascent RNA base pairing within and upon exit from RNA polymerases (Pols) transcriptome wide in living yeast cells. Monitoring each nucleotide’s base pairing activity during transcription, CoSTseq reveals predominantly rapid pairing—within 25 bp of transcription after addition to the nascent chain. Moreover, ∼23% of rRNA nucleotides attain their final base pairing state near Pol I, while most other nucleotides must undergo changes in pairing status during later steps of ribosome biogenesis. We show that helicases act immediately to remodel structures across the rDNA locus to facilitate ribosome biogenesis. By contrast, nascent pre-mRNAs attain local structures indistinguishable from mature mRNAs, suggesting that refolding behind elongating ribosomes resembles co-transcriptional folding behind Pol II.
