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| Title | Mechanistic insights into RNA chaperoning by Ro60 and La autoantigens. |
|---|---|
| Journal, issue, pages | Cell, Vol. 189, Issue 4, Page 1135-1152.e23, Year 2026 |
| Publish date | Feb 19, 2026 |
 Authors | Hyeyeon Nam / Justin C Deme / Soyeong Sim / Marco Boccitto / Susan M Lea / Sandra L Wolin /  |
| PubMed Abstract | Although ATP-independent chaperones assist RNA folding, the mechanisms by which they function remain elusive. Here, we demonstrate how two RNA chaperones collaborate to unfold misfolded noncoding ...Although ATP-independent chaperones assist RNA folding, the mechanisms by which they function remain elusive. Here, we demonstrate how two RNA chaperones collaborate to unfold misfolded noncoding RNAs (ncRNAs). The ring-shaped Ro60 protein binds the ends of misfolded ncRNAs in its cavity, whereas La stabilizes nascent ncRNAs and assists their folding. Using cryo-electron microscopy to resolve the structure of a misfolded RNA complexed with Ro60 and La, we show that La cradles the Ro60 ribonucleoprotein (RNP), with its N-terminal domain binding the RNA 3' end after it passes through the Ro60 cavity, while its C-terminal domain destabilizes structures in the misfolded RNA body. Using selective 2'-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP), we show that La and Ro60 function synergistically to unfold non-native structures. As the RNAs bound by Ro60 and La include both ncRNA precursors and ncRNAs with oligouridine tails, this RNA chaperone machine may function widely to recognize misfolded and otherwise aberrant ncRNAs and assist their unfolding. |
 External links | Cell / PubMed:41610850 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.7 - 3.5 Å |
| Structure data |  EMDB-49327: Cryo-EM structure of Ro60/U-tailed 5S rRNA complex EMDB-49328, PDB-9nen: EMDB-49329, PDB-9nep:  EMDB-49353: Cryo-EM structure of Ro60/La/truncated misfolded human pre-5S rRNA complex with Fab, consensus map  EMDB-49354: Cryo-EM structure of Ro60/La/truncated misfolded human pre-5S rRNA complex with Fab, focused map EMDB-49355, PDB-9nf8:  EMDB-49357: Cryo-EM structure of Ro60/La/minimal misfolded pre-5S rRNA complex with Fab, consensus map  EMDB-49358: Cryo-EM structure of Ro60/La/minimal misfolded pre-5S rRNA complex with Fab, N-term La/Fab focused map  EMDB-49359: Cryo-EM structure of Ro60/La/minimal misfolded pre-5S rRNA complex with Fab, C-term La focused map EMDB-49360, PDB-9nfa: |
| Chemicals |  ChemComp-MG: |
| Source |
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 Keywords | RNA BINDING PROTEIN/RNA / Ro60 autoantigen / RNA chaperone / RNA folding / RNA BINDING PROTEIN / RNA BINDING PROTEIN-RNA complex / La autoantigen |
homo sapiens (human)
xenopus laevis (African clawed frog)