6m8q | pdb_00006m8q

Cleavage and Polyadenylation Specificity Factor Subunit 3 (CPSF3) in complex with NVP-LTM531

Structural highlights

6m8q is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	JBG, PO4, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4]

References

↑ Kaufmann I, Martin G, Friedlein A, Langen H, Keller W. Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase. EMBO J. 2004 Feb 11;23(3):616-26. Epub 2004 Jan 29. PMID:14749727 doi:https://dx.doi.org/10.1038/sj.emboj.7600070
↑ Ryan K, Calvo O, Manley JL. Evidence that polyadenylation factor CPSF-73 is the mRNA 3' processing endonuclease. RNA. 2004 Apr;10(4):565-73. PMID:15037765
↑ Kolev NG, Yario TA, Benson E, Steitz JA. Conserved motifs in both CPSF73 and CPSF100 are required to assemble the active endonuclease for histone mRNA 3'-end maturation. EMBO Rep. 2008 Oct;9(10):1013-8. doi: 10.1038/embor.2008.146. Epub 2008 Aug 8. PMID:18688255 doi:https://dx.doi.org/10.1038/embor.2008.146
↑ Mandel CR, Kaneko S, Zhang H, Gebauer D, Vethantham V, Manley JL, Tong L. Polyadenylation factor CPSF-73 is the pre-mRNA 3'-end-processing endonuclease. Nature. 2006 Dec 14;444(7121):953-6. Epub 2006 Nov 26. PMID:17128255 doi:10.1038/nature05363

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OCA

[1] Kaufmann I, Martin G, Friedlein A, Langen H, Keller W. Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase. EMBO J. 2004 Feb 11;23(3):616-26. Epub 2004 Jan 29. PMID:14749727 doi:https://dx.doi.org/10.1038/sj.emboj.7600070

[2] Ryan K, Calvo O, Manley JL. Evidence that polyadenylation factor CPSF-73 is the mRNA 3' processing endonuclease. RNA. 2004 Apr;10(4):565-73. PMID:15037765

[3] Kolev NG, Yario TA, Benson E, Steitz JA. Conserved motifs in both CPSF73 and CPSF100 are required to assemble the active endonuclease for histone mRNA 3'-end maturation. EMBO Rep. 2008 Oct;9(10):1013-8. doi: 10.1038/embor.2008.146. Epub 2008 Aug 8. PMID:18688255 doi:https://dx.doi.org/10.1038/embor.2008.146

[4] Mandel CR, Kaneko S, Zhang H, Gebauer D, Vethantham V, Manley JL, Tong L. Polyadenylation factor CPSF-73 is the pre-mRNA 3'-end-processing endonuclease. Nature. 2006 Dec 14;444(7121):953-6. Epub 2006 Nov 26. PMID:17128255 doi:10.1038/nature05363

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6m8q | pdb_00006m8q

Cleavage and Polyadenylation Specificity Factor Subunit 3 (CPSF3) in complex with NVP-LTM531

Structural highlights

Function

References

Contents

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