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==CRYO-EM STRUCTURE OF HUMAN U7 SNRNP WITH METHYLATED noncleavable H2A* SUBSTRATE PRE-MRNA (FOCUS MAP)==
<StructureSection load='9ngo' size='340' side='right'caption='[[9ngo]], [[Resolution|resolution]] 3.01&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9ngo]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9NGO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9NGO FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.01&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9ngo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ngo OCA], [https://pdbe.org/9ngo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ngo RCSB], [https://www.ebi.ac.uk/pdbsum/9ngo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ngo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CPSF3_HUMAN CPSF3_HUMAN] Component of the cleavage and polyadenylation specificity factor (CPSF) complex that play a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. Has endonuclease activity, and functions as mRNA 3'-end-processing endonuclease. Also involved in the histone 3'-end pre-mRNA processing. U7 snRNP-dependent protein that induces both the 3'-endoribonucleolytic cleavage of histone pre-mRNAs and acts as a 5' to 3' exonuclease for degrading the subsequent downstream cleavage product (DCP) of mature histone mRNAs. Cleavage occurs after the 5'-ACCCA-3' sequence in the histone pre-mRNA leaving a 3'hydroxyl group on the upstream fragment containing the stem loop (SL) and 5' phosphate on the downstream cleavage product (DCP) starting with CU nucleotides. The U7-dependent 5' to 3' exonuclease activity is processive and degrades the DCP RNA substrate even after complete removal of the U7-binding site. Binds to the downstream cleavage product (DCP) of histone pre-mRNAs and the cleaved DCP RNA substrate in a U7 snRNP dependent manner.<ref>PMID:14749727</ref> <ref>PMID:15037765</ref> <ref>PMID:18688255</ref> <ref>PMID:17128255</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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-beta-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.

An N-terminal helix of Lsm11 stabilizes CPSF73 in U7 snRNP for histone pre-mRNA 3'-end processing.,Desotell A, Marzluff WF, Dominski Z, Tong L Nucleic Acids Res. 2026 Jan 5;54(1):gkaf1442. doi: 10.1093/nar/gkaf1442. PMID:41495886<ref>PMID:41495886</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9ngo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Desotell A]]
[[Category: Tong L]]