6v4x

Structural highlights

Function

[LSM10_HUMAN] Appears to function in the U7 snRNP complex that is involved in histone 3'-end processing. Increases U7 snRNA levels but not histone 3'-end pre-mRNA processing activity, when overexpressed. Required for cell cycle progression from G1 to S phases. Binds specifically to U7 snRNA. Binds to the downstream cleavage product (DCP) of histone pre-mRNA in a U7 snRNP dependent manner.^[1] [RUXF_HUMAN] Appears to function in the U7 snRNP complex that is involved in histone 3'-end processing. Associated with snRNP U1, U2, U4/U6 and U5. [LSM11_HUMAN] Component of the U7 snRNP complex that is involved in the histone 3'-end pre-mRNA processing (By similarity). Increases U7 snRNA levels but not histone 3'-end pre-mRNA processing activity, when overexpressed. Required for cell cycle progression from G1 to S phases. Binds specifically to the Sm-binding site of U7 snRNA.^[2] [CPSF2_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. Involved in the histone 3' end pre-mRNA processing.^{[3] [4]} [RSMB_HUMAN] Appears to function in the U7 snRNP complex that is involved in histone 3'-end processing. Associated with snRNP U1, U2, U4/U6 and U5. May have a functional role in the pre-mRNA splicing or in snRNP structure. Binds to the downstream cleavage product (DCP) of histone pre-mRNA in a U7 snRNP dependent manner (By similarity). [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.^{[5] [6] [7] [8]} [SMD3_HUMAN] Appears to function in the U7 snRNP complex that is involved in histone 3'-end processing. Binds to the downstream cleavage product (DCP) of histone pre-mRNA in a U7 snRNP dependent manner.^[9] [RUXE_HUMAN] Appears to function in the U7 snRNP complex that is involved in histone 3'-end processing. Associated with snRNP U1, U2, U4/U6 and U5. [SYMPK_HUMAN] Scaffold protein that functions as a component of a multimolecular complex involved in histone mRNA 3'-end processing. Specific component of the tight junction (TJ) plaque, but might not be an exclusively junctional component. May have a house-keeping rule. Is involved in pre-mRNA polyadenylation. Enhances SSU72 phosphatase activity.^{[10] [11]} [RUXG_HUMAN] Appears to function in the U7 snRNP complex that is involved in histone 3'-end processing. Associated with snRNP U1, U2, U4/U6 and U5.

See Also

• Nucleoprotein 3D structures
• Symplekin

References

1. ↑ Wagner EJ, Marzluff WF. ZFP100, a component of the active U7 snRNP limiting for histone pre-mRNA processing, is required for entry into S phase. Mol Cell Biol. 2006 Sep;26(17):6702-12. PMID:16914750 doi:http://dx.doi.org/26/17/6702
2. ↑ Wagner EJ, Marzluff WF. ZFP100, a component of the active U7 snRNP limiting for histone pre-mRNA processing, is required for entry into S phase. Mol Cell Biol. 2006 Sep;26(17):6702-12. PMID:16914750 doi:http://dx.doi.org/26/17/6702
3. ↑ 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:http://dx.doi.org/10.1038/sj.emboj.7600070
4. ↑ 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:http://dx.doi.org/10.1038/embor.2008.146
5. ↑ 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:http://dx.doi.org/10.1038/sj.emboj.7600070
6. ↑ 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
7. ↑ 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:http://dx.doi.org/10.1038/embor.2008.146
8. ↑ 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
9. ↑ Pillai RS, Will CL, Luhrmann R, Schumperli D, Muller B. Purified U7 snRNPs lack the Sm proteins D1 and D2 but contain Lsm10, a new 14 kDa Sm D1-like protein. EMBO J. 2001 Oct 1;20(19):5470-9. PMID:11574479 doi:10.1093/emboj/20.19.5470
10. ↑ Kolev NG, Steitz JA. Symplekin and multiple other polyadenylation factors participate in 3'-end maturation of histone mRNAs. Genes Dev. 2005 Nov 1;19(21):2583-92. Epub 2005 Oct 17. PMID:16230528 doi:10.1101/gad.1371105
11. ↑ Xiang K, Nagaike T, Xiang S, Kilic T, Beh MM, Manley JL, Tong L. Crystal structure of the human symplekin-Ssu72-CTD phosphopeptide complex. Nature. 2010 Sep 22. PMID:20861839 doi:10.1038/nature09391
12. ↑ Sun Y, Zhang Y, Aik WS, Yang XC, Marzluff WF, Walz T, Dominski Z, Tong L. Structure of an active human histone pre-mRNA 3'-end processing machinery. Science. 2020 Feb 7;367(6478):700-703. doi: 10.1126/science.aaz7758. PMID:32029631 doi:http://dx.doi.org/10.1126/science.aaz7758