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

Fibrillarin (FBL) promotes switch (S)-S DNA synapsis at the IgH locus during class switch recombination (CSR) without altering DNA cleavage, requiring both RNA-binding and catalytic activity.

• Why it matters: The mechanism by which the RNA 2'-O-methyltransferase FBL regulates antibody diversification is unclear, particularly how it coordinates RNA processing with IgH synapsis during CSR.
• What they did: In B cells, FBL and MED19 regulate snoRNAs that guide 2'-O-methylation of -germline transcripts (-GLTs), which form nuclear condensates; FBL methylation controls condensate protein composition and fusion dynamics.
• The result: Low WDR74 expression in B cells promotes - and -GLT condensate fusion, enhancing S-S synapsis, CSR, and IgH/c-Myc translocation, potentially linked to poor myeloma prognosis.

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