biostudies-literatureClarke BPNIAID NIH HHSNCI NIH HHSNational Institutes of HealthNIH HHSNIGMS NIH HHSRP91432https://www.ebi.ac.uk/biostudies/studies/S-EPMC11405014biostudies-literatureUnknown12In eukaryotes, RNAs transcribed by RNA Pol II are modified at the 5' end with a 7-methylguanosine (m⁷G) cap, which is recognized by the nuclear cap binding complex (CBC). The CBC plays multiple important roles in mRNA metabolism, including transcription, splicing, polyadenylation, and export. It promotes mRNA export through direct interaction with a key mRNA export factor, ALYREF, which in turn links the TRanscription and EXport (TREX) complex to the 5' end of mRNA. However, the molecular mechanism for CBC-mediated recruitment of the mRNA export machinery is not well understood. Here, we present the first structure of the CBC in complex with an mRNA export factor, ALYREF. The cryo-EM structure of CBC-ALYREF reveals that the RRM domain of ALYREF makes direct contact with both theeLifeCryo-EM structure of the CBC-ALYREF complex.PMC11405014T32 CA119925S10 OD030292R35 GM133743R01 AI184975Mei MHill PSXie YClarke BPAngelos AERen YfalseCryo-EM structure of the CBC-ALYREF complex.In eukaryotes, RNAs transcribed by RNA Pol II are modified at the 5' end with a 7-methylguanosine (m⁷G) cap, which is recognized by the nuclear cap binding complex (CBC). The CBC plays multiple important roles in mRNA metabolism, including transcription, splicing, polyadenylation, and export. It promotes mRNA export through direct interaction with a key mRNA export factor, ALYREF, which in turn links the TRanscription and EXport (TREX) complex to the 5' end of mRNA. However, the molecular mechanism for CBC-mediated recruitment of the mRNA export machinery is not well understood. Here, we present the first structure of the CBC in complex with an mRNA export factor, ALYREF. The cryo-EM structure of CBC-ALYREF reveals that the RRM domain of ALYREF makes direct contact with both the2024-01-01T00:00:00Z2024 Sep2026-06-01T10:08:15.834Z2025-04-04T08:22:22.45ZS-EPMC114050143928294910.7554/eLife.91432