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6dnh

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Revision as of 20:56, 6 March 2020

Cryo-EM structure of human CPSF-160-WDR33-CPSF-30-PAS RNA complex at 3.4 A resolution

6dnh, resolution 3.40Å

Structural highlights

6dnh is a 4 chain structure with sequence from Human. This structure supersedes the now removed PDB entry 6bll. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	CPSF1, CPSF160 (HUMAN), WDR33, WDC146 (HUMAN), CPSF4, CPSF30, NAR, NEB1 (HUMAN)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CPSF1_HUMAN] Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays 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. This subunit is involved in the RNA recognition step of the polyadenylation reaction.^[1] [CPSF4_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. CPSF4 binds RNA polymers with a preference for poly(U).^[2] ^[3] [WDR33_HUMAN] Essential for both cleavage and polyadenylation of pre-mRNA 3' ends.^[4]

Publication Abstract from PubMed

Nearly all eukaryotic messenger RNA precursors must undergo cleavage and polyadenylation at their 3'-end for maturation. A crucial step in this process is the recognition of the AAUAAA polyadenylation signal (PAS), and the molecular mechanism of this recognition has been a long-standing problem. Here, we report the cryo-electron microscopy structure of a quaternary complex of human CPSF-160, WDR33, CPSF-30, and an AAUAAA RNA at 3.4-A resolution. Strikingly, the AAUAAA PAS assumes an unusual conformation that allows this short motif to be bound directly by both CPSF-30 and WDR33. The A1 and A2 bases are recognized specifically by zinc finger 2 (ZF2) of CPSF-30 and the A4 and A5 bases by ZF3. Interestingly, the U3 and A6 bases form an intramolecular Hoogsteen base pair and directly contact WDR33. CPSF-160 functions as an essential scaffold and preorganizes CPSF-30 and WDR33 for high-affinity binding to AAUAAA. Our findings provide an elegant molecular explanation for how PAS sequences are recognized for mRNA 3'-end formation.

Molecular basis for the recognition of the human AAUAAA polyadenylation signal.,Sun Y, Zhang Y, Hamilton K, Manley JL, Shi Y, Walz T, Tong L Proc Natl Acad Sci U S A. 2017 Dec 5. pii: 1718723115. doi:, 10.1073/pnas.1718723115. PMID:29208711^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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:http://dx.doi.org/10.1038/sj.emboj.7600070
↑ Barabino SM, Hubner W, Jenny A, Minvielle-Sebastia L, Keller W. The 30-kD subunit of mammalian cleavage and polyadenylation specificity factor and its yeast homolog are RNA-binding zinc finger proteins. Genes Dev. 1997 Jul 1;11(13):1703-16. PMID:9224719
↑ 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
↑ Shi Y, Di Giammartino DC, Taylor D, Sarkeshik A, Rice WJ, Yates JR 3rd, Frank J, Manley JL. Molecular architecture of the human pre-mRNA 3' processing complex. Mol Cell. 2009 Feb 13;33(3):365-76. doi: 10.1016/j.molcel.2008.12.028. PMID:19217410 doi:http://dx.doi.org/10.1016/j.molcel.2008.12.028
↑ Sun Y, Zhang Y, Hamilton K, Manley JL, Shi Y, Walz T, Tong L. Molecular basis for the recognition of the human AAUAAA polyadenylation signal. Proc Natl Acad Sci U S A. 2017 Dec 5. pii: 1718723115. doi:, 10.1073/pnas.1718723115. PMID:29208711 doi:http://dx.doi.org/10.1073/pnas.1718723115

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6dnh"

@@ Line 1: / Line 1: @@
 ==Cryo-EM structure of human CPSF-160-WDR33-CPSF-30-PAS RNA complex at 3.4 A resolution==
-<StructureSection load='6dnh' size='340' side='right'caption='[[6dnh]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
+<SX load='6dnh' size='340' side='right' viewer='molstar' caption='[[6dnh]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[6dnh]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=6bll 6bll]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DNH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DNH FirstGlance]. <br>
@@ Line 22: / Line 22: @@
 <references/>
 __TOC__
-</StructureSection>
+</SX>
 [[Category: Human]]
 [[Category: Large Structures]]

6dnh

From Proteopedia

Revision as of 20:56, 6 March 2020

Cryo-EM structure of human CPSF-160-WDR33-CPSF-30-PAS RNA complex at 3.4 A resolution

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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