{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe nuclear cap‐binding complex (CBC) is central to the processing of RNA polymerase II transcripts by specifically recognizing the 7‐methylguanosine (m7G) cap. Structural and biochemical studies have revealed that the canonical CBC is composed of two main subunits—NCBP1 and NCBP2—with the cap recognition process involving dramatic cap‐induced conformational changes, cooperative folding, and aromatic stacking interactions that secure the methylated guanosine base."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, investigations into transcriptional regulation and mRNA processing have shown that the CBC participates in multiple nuclear processes—including pre-mRNA splicing, 3' end formation (notably for replication-dependent histone mRNAs), and subsequent RNA export—with the spatial organization of CBC-containing foci further underscoring its integration in RNA biogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFocused studies on the individual contributions of CBC subunits have revealed that despite being a canonical component, NCBP2 appears to be functionally redundant under steady‐state conditions. For example, while NCBP1 is indispensable for cell viability and polyadenylated RNA export, loss of NCBP2 is compensated by the activity of alternative cap-binding proteins such as NCBP3, which in association with NCBP1 forms an alternative CBC."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, in the context of human cancers such as head and neck squamous cell carcinoma, aberrations in m7G-related cap-binding gene expression—specifically lower levels of NCBP2 paired with higher expression of factors like EIF4E3—correlate with distinct immune cell infiltrates, modulation of downstream gene expression, and an improved response to immunotherapy, thereby suggesting that NCBP2 may influence the “cold-to-hot” tumor transition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Catherine Mazza, Alexandra Segref, Iain W Mattaj, et al. 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