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-Structure paper
| タイトル | An N-terminal helix of Lsm11 stabilizes CPSF73 in U7 snRNP for histone pre-mRNA 3'-end processing. |
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| ジャーナル・号・ページ | Nucleic Acids Res, Vol. 54, Issue 1, Year 2026 |
| 掲載日 | 2026年1月5日 |
著者 | Anthony Desotell / William F Marzluff / Zbigniew Dominski / Liang Tong / ![]() |
| PubMed 要旨 | 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 ...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 that a previously uninterpreted EM density for a small helix at the CPSF73-CPSF100 interface belonged to the C-terminal end of CstF77, copurified from insect cells and highly conserved among CstF77 homologs. This CstF77 binding site had a small effect on the cleavage activity of U7 snRNP. Overall, our studies have revealed the importance of the conserved helix in the Lsm11 N-terminal extension for U7 snRNP, provided structural evidence that CPSF73 can achieve an open, active conformation without RNA binding in its active site, and identified a previously unknown binding site for CstF77 in CPSF100. |
リンク | Nucleic Acids Res / PubMed:41495886 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.82 - 3.85 Å |
| 構造データ | EMDB-49161: CryoEM structure of U7 Sm Ring in complex with symplekin N-terminal domain EMDB-49206, PDB-9nb1: EMDB-49389: CRYO-EM STRUCTURE OF HUMAN U7 SNRNP WITH METHYLATED H2A* SUBSTRATE PRE-MRNA FOCUS MAP EMDB-49402, PDB-9nh5: EMDB-49403, PDB-9nh6: |
| 化合物 | ![]() ChemComp-ZN: |
| 由来 |
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キーワード | RNA BINDING PROTEIN/RNA / Symplekin / 3' end processing / U7 snRNP / Histone pre-mRNA / RNA BINDING PROTEIN / RNA BINDING PROTEIN-RNA complex / Methylated RNA |
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