biostudies-literatureDesotell ANIHNIH HHSNIGMS NIH HHSgkaf1442https://www.ebi.ac.uk/biostudies/studies/S-EPMC12774660biostudies-literatureUnknown54(1)The U7 snRNP (small nuclear ribonucleoprotein) is responsible for the 3'-end processing of replication-dependent histone messenger RNA precursors (pre-mRNAs). A helix in the Lsm11 N-terminal extension contacts the metallo-β-lactamase domain of the U7 snRNP endonuclease CPSF73. We mutated or deleted this helix and found that the mutant machineries had substantially reduced cleavage activity toward the pre-mRNA. Our cryo-electron microscopy (cryo-EM) studies indicated that the helix was important for helping to hold CPSF73 in its correct position for the cleavage reaction. We also reconstituted a wild-type U7 snRNP in complex with a methylated, noncleavable pre-mRNA. We observed that CPSF73 could achieve an open conformation independent of RNA binding to its active site. Finally, we found thNucleic acids researchAn N-terminal helix of Lsm11 stabilizes CPSF73 in U7 snRNP for histone pre-mRNA 3'-end processing.PMC12774660R35 GM118093R35GM118093Marzluff WFTong LDominski ZDesotell AfalseAn N-terminal helix of Lsm11 stabilizes CPSF73 in U7 snRNP for histone pre-mRNA 3'-end processing.The U7 snRNP (small nuclear ribonucleoprotein) is responsible for the 3'-end processing of replication-dependent histone messenger RNA precursors (pre-mRNAs). A helix in the Lsm11 N-terminal extension contacts the metallo-β-lactamase domain of the U7 snRNP endonuclease CPSF73. We mutated or deleted this helix and found that the mutant machineries had substantially reduced cleavage activity toward the pre-mRNA. Our cryo-electron microscopy (cryo-EM) studies indicated that the helix was important for helping to hold CPSF73 in its correct position for the cleavage reaction. We also reconstituted a wild-type U7 snRNP in complex with a methylated, noncleavable pre-mRNA. We observed that CPSF73 could achieve an open conformation independent of RNA binding to its active site. Finally, we found th2026-01-01T00:00:00Z2026 Jan2026-07-15T09:12:48.928Z2026-07-02T03:08:59.707ZS-EPMC127746604149588610.1093/nar/gkaf1442