CPSF4

Cleavage and polyadenylation specificity factor subunit 4 is a protein that in humans is encoded by the CPSF4 gene.[5][6][7]

CPSF4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2D9N, 2RHK
Identifiers
Aliases	CPSF4, CPSF30, NAR, NEB1, NEB-1, cleavage and polyadenylation specific factor 4
External IDs	OMIM: 603052 MGI: 1861602 HomoloGene: 38216 GeneCards: CPSF4
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7q22.1 Start 99,438,922 bp[1] End 99,457,373 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5|5 G2 Start 145,167,213 bp[2] End 145,182,041 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • nucleic acid binding • zinc ion binding • GO:0001948 protein binding • metal ion binding • endoribonuclease activity • RNA binding Cellular component • mRNA cleavage and polyadenylation specificity factor complex • cell nucleus • nucleoplasm • intracellular membrane-bounded organelle Biological process • mRNA processing • modification by virus of host mRNA processing • GO:0022415 viral process • tRNA splicing, via endonucleolytic cleavage and ligation • mRNA splicing, via spliceosome • termination of RNA polymerase II transcription • mRNA polyadenylation • mRNA export from nucleus • mRNA 3'-end processing • RNA phosphodiester bond hydrolysis, endonucleolytic • pre-mRNA cleavage required for polyadenylation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	10898	54188
Ensembl	ENSG00000160917	ENSMUSG00000029625
UniProt	O95639	Q8BQZ5
RefSeq (mRNA)	NM_001081559 NM_006693 NM_001318160 NM_001318161 NM_001318162	NM_001291248 NM_001291249 NM_178576 NM_001374716
RefSeq (protein)	NP_001075028 NP_001305089 NP_001305090 NP_001305091 NP_006684	NP_001278177 NP_001278178 NP_848671 NP_001361645
Location (UCSC)	Chr 7: 99.44 – 99.46 Mb	Chr 5: 145.17 – 145.18 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Inhibition of the nuclear export of poly(A)-containing mRNAs caused by the influenza A virus NS1 protein requires its effector domain. The NS1 effector domain functionally interacts with the cellular 30 kDa subunit of cleavage and polyadenylation specific factor 4, an essential component of the 3' end processing machinery of cellular pre-mRNAs.

In influenza virus-infected cells, the NS1 protein is physically associated with cleavage and polyadenylation specific factor 4, 30kD subunit. Binding of the NS1 protein to the 30 kDa protein in vitro prevents CPSF binding to the RNA substrate and inhibits 3' end cleavage and polyadenylation of host pre-mRNAs.

Thus the NS1 protein selectively inhibits the nuclear export of cellular, and not viral, mRNAs. Multiple alternatively spliced transcript variants that encode different isoforms have been described for this gene.[7]

References

1. GRCh38: Ensembl release 89: ENSG00000160917 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000029625 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Nemeroff ME, Barabino SM, Li Y, Keller W, Krug RM (Jul 1998). "Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs". Mol Cell. 1 (7): 991–1000. doi:10.1016/S1097-2765(00)80099-4. PMID 9651582.
6. Barabino SM, Hubner W, Jenny A, Minvielle-Sebastia L, Keller W (Aug 1997). "The 30-kD subunit of mammalian cleavage and polyadenylation specificity factor and its yeast homolog are RNA-binding zinc finger proteins". Genes Dev. 11 (13): 1703–16. doi:10.1101/gad.11.13.1703. PMID 9224719.
7. "Entrez Gene: CPSF4 cleavage and polyadenylation specific factor 4, 30kDa".

Further reading

• Jenny A, Hauri HP, Keller W (1994). "Characterization of cleavage and polyadenylation specificity factor and cloning of its 100-kilodalton subunit". Mol. Cell. Biol. 14 (12): 8183–90. doi:10.1128/MCB.14.12.8183. PMC 359357. PMID 7969155.
• Thuresson AC, Aström J, Aström A, et al. (1994). "Multiple forms of poly(A) polymerases in human cells". Proc. Natl. Acad. Sci. U.S.A. 91 (3): 979–83. doi:10.1073/pnas.91.3.979. PMC 521437. PMID 8302877.
• Hillier LD, Lennon G, Becker M, et al. (1997). "Generation and analysis of 280,000 human expressed sequence tags". Genome Res. 6 (9): 807–28. doi:10.1101/gr.6.9.807. PMID 8889549.
• McCracken S, Fong N, Yankulov K, et al. (1997). "The C-terminal domain of RNA polymerase II couples mRNA processing to transcription". Nature. 385 (6614): 357–61. doi:10.1038/385357a0. PMID 9002523. S2CID 4307073.
• de Vries H, Rüegsegger U, Hübner W, et al. (2000). "Human pre-mRNA cleavage factor II(m) contains homologs of yeast proteins and bridges two other cleavage factors". EMBO J. 19 (21): 5895–904. doi:10.1093/emboj/19.21.5895. PMC 305781. PMID 11060040.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Scherer SW, Cheung J, MacDonald JR, et al. (2003). "Human chromosome 7: DNA sequence and biology". Science. 300 (5620): 767–72. doi:10.1126/science.1083423. PMC 2882961. PMID 12690205.
• Kaufmann I, Martin G, Friedlein A, et al. (2005). "Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase". EMBO J. 23 (3): 616–26. doi:10.1038/sj.emboj.7600070. PMC 1271804. PMID 14749727.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
• Oh JH, Yang JO, Hahn Y, et al. (2006). "Transcriptome analysis of human gastric cancer". Mamm. Genome. 16 (12): 942–54. doi:10.1007/s00335-005-0075-2. PMID 16341674. S2CID 69278.
• Twu KY, Kuo RL, Marklund J, Krug RM (2007). "The H5N1 influenza virus NS genes selected after 1998 enhance virus replication in mammalian cells". J. Virol. 81 (15): 8112–21. doi:10.1128/JVI.00006-07. PMC 1951328. PMID 17522219.

External links

• Human CPSF4 genome location and CPSF4 gene details page in the UCSC Genome Browser.
• Overview of all the structural information available in the PDB for UniProt: O95639 (Cleavage and polyadenylation specificity factor subunit 4) at the PDBe-KB.