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

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 α-germline transcripts (α-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 μ- and α-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.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-11-06
DOI
https://doi.org/10.64898/2026.11.05.761835
Primary Topic
Genomics and Chromatin Dynamics
Type
preprint

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preprint

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

Tasuku Honjo, Takahito Moriwaki, Hidetaka Kosako, Hodaka Fujii et al.
1 links
bioRxiv (Cold Spring Harbor Laboratory)
Genomics and Chromatin Dynamics
preprint

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

Tasuku Honjo, Takahito Moriwaki, Hidetaka Kosako, Hodaka Fujii, Kei Iida, Xi Chen, Afzal Husain, Luthfi Lulul Ulum, Takanori Oyoshi, Toshitsugu Fujita, Maki Kobayashi, Ziwei Yin, Wencong Wang, Kanon Omura, Jianliang Xu
preprint en

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 α-germline transcripts (α-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 μ- and α-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.

bioRxiv (Cold Spring Harbor Laboratory)
Shizuoka University (JP), Hirosaki University (JP), Kyoto University (JP), Research Institute of Green Science and Technology, Shizuoka University (JP), Center for Cancer Immunotherapy and Immunobiology, Kyoto University (JP), Institute of Advanced Medical Sciences, Tokushima University (JP), Institute of Photonics and Human Health Frontier, Tokushima University (JP), Kindai University (JP), Tokushima University (JP)
Japan Society for the Promotion of Science
Genomics and Chromatin Dynamics
DOIOpen Access PDFOpenAlex
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