2'-O-Methylated ncRNA condensates form a recombination center for IgH synapsis

Authors

Kobayashi, M., Xu, J., Husain, A., Moriwaki, T., Yin, Z., Chen, X., Wang, W., Fujita, T., Fujii, H., Ulum, L. L., Oyoshi, T., Omura, K., Iida, K., Kosako, H., Honjo, T.

Abstract

How fibrillarin (FBL), an RNA 2'-O-methyltransferase, regulates antibody diversification remains unclear. This study demonstrated that FBL promotes switch (S)-S DNA synapsis at the IgH locus during class switch recombination (CSR), without affecting DNA cleavage. Both RNA-binding and catalytic activities of FBL were essential for CSR. Moreover, MED19 supported DNA cleavage and synapsis by regulating snoRNAs that guide 2'-O-methylation. Mechanistically, FBL methylated -germline transcripts (-GLTs), cis-acting noncoding RNAs forming nuclear condensates harboring machinery for RNA processing, RNP remodeling, and chromatin dynamics. FBL-mediated 2'-O-methylation governed condensate protein composition. FBL suppression aberrantly enriched nucleolar proteins, including WDR74. Crucially, low WDR74 expression in B cells promoted - and -GLT condensate fusion, thereby enhancing S-S synapsis, CSR, and IgH/c-Myc translocation, potentially contributing to poor myeloma prognosis. Altogether, our findings revealed that RNA 2'-O-methylation dictates GLT condensate composition and fusion dynamics to establish a recombination center, driving genomic DNA synapsis in B cells.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 07 Nov 2026.

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