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| Title | Interprotomer communication and functional asymmetry in H/ACA snoRNPs. |
|---|---|
| Journal, issue, pages | Proc Natl Acad Sci U S A, Vol. 122, Issue 51, Page e2514683122, Year 2025 |
| Publish date | Dec 23, 2025 |
 Authors | Hemendra Singh Panwar / Timothy J Vos / Xiaoyan Xie / H Josh Jang / Hyoungjoo Lee / Ryan D Sheldon / Evan J Worden / Ute Kothe /   |
| PubMed Abstract | H/ACA small nucleolar ribonucleoproteins (H/ACA snoRNPs) facilitate essential cellular processes such as RNA modification, folding, and stability. Here, we present multiple cryo-EM structures of ...H/ACA small nucleolar ribonucleoproteins (H/ACA snoRNPs) facilitate essential cellular processes such as RNA modification, folding, and stability. Here, we present multiple cryo-EM structures of endogenous insect H/ACA snoRNPs containing two protomers assembled on a two-hairpin H/ACA snoRNA. By characterizing key protein-protein and protein-RNA interactions, we reveal the coordination of pseudouridylation activity across the two protomers which explains the predominance of two-hairpin structures in eukaryotic H/ACA snoRNAs. Moreover, we found that several mutations in H/ACA proteins associated with dyskeratosis congenita (DC) directly impair pseudouridine formation suggesting how these mutations disrupt RNA modification and ribosome biogenesis in this disease. Additionally, we uncover coordinated structural changes between Nop10, Nhp2, and the N-terminal extensions of Cbf5 in the 3' protomer that resemble active and inactive conformations and may regulate H/ACA snoRNP activity. In summary, this study provides detailed insight into the structure and function of RNA modification-competent H/ACA snoRNPs, which play pivotal roles in cellular processes including ribosome biogenesis, rRNA folding, (m)RNA modification, and telomere maintenance. |
 External links | Proc Natl Acad Sci U S A / PubMed:41410763 |
| Methods | EM (single particle) |
| Resolution | 2.86 - 3.23 Å |
| Structure data | EMDB-72897, PDB-9yfl: EMDB-72898, PDB-9yfm:  EMDB-72899: insect H/ACA snoRNP class II Consensus map  EMDB-72900: insect class II H/ACA snoRNP - Focused map 3'half  EMDB-72901: insect class II H/ACA - Focused map 5' half EMDB-72902, PDB-9yfn: EMDB-72903, PDB-9yfo: |
| Source |
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 Keywords | RNA BINDING PROTEIN / Pseudouridine synthase / enzyme complex / snoRNA / snoRNP |
trichoplusia ni (cabbage looper)