CPSF4 explained

Cleavage and polyadenylation specificity factor subunit 4 is a protein that in humans is encoded by the CPSF4 gene.^{[1] [2] [3]}

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.

Further reading

• Jenny A, Hauri HP, Keller W . Characterization of cleavage and polyadenylation specificity factor and cloning of its 100-kilodalton subunit. . Mol. Cell. Biol. . 14 . 12 . 8183–90 . 1994 . 7969155 . 10.1128/MCB.14.12.8183. 359357 .
• Thuresson AC, Aström J, Aström A . Multiple forms of poly(A) polymerases in human cells. . Proc. Natl. Acad. Sci. U.S.A. . 91 . 3 . 979–83 . 1994 . 8302877 . 10.1073/pnas.91.3.979 . 521437 . 1994PNAS...91..979T . etal. free .
• Hillier LD, Lennon G, Becker M . Generation and analysis of 280,000 human expressed sequence tags. . Genome Res. . 6 . 9 . 807–28 . 1997 . 8889549 . 10.1101/gr.6.9.807 . etal. free .
• McCracken S, Fong N, Yankulov K . The C-terminal domain of RNA polymerase II couples mRNA processing to transcription. . Nature . 385 . 6614 . 357–61 . 1997 . 9002523 . 10.1038/385357a0 . 1997Natur.385..357M . 4307073 . etal.
• de Vries H, Rüegsegger U, Hübner W . Human pre-mRNA cleavage factor II(m) contains homologs of yeast proteins and bridges two other cleavage factors. . EMBO J. . 19 . 21 . 5895–904 . 2000 . 11060040 . 10.1093/emboj/19.21.5895 . 305781 . etal.
• Strausberg RL, Feingold EA, Grouse LH . 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 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Scherer SW, Cheung J, MacDonald JR . Human chromosome 7: DNA sequence and biology. . Science . 300 . 5620 . 767–72 . 2003 . 12690205 . 2882961 . 10.1126/science.1083423 . 2003Sci...300..767S . etal.
• Kaufmann I, Martin G, Friedlein A . 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 . 2005 . 14749727 . 10.1038/sj.emboj.7600070 . 1271804 . etal.
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Rual JF, Venkatesan K, Hao T . Towards a proteome-scale map of the human protein-protein interaction network. . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 . etal.
• Oh JH, Yang JO, Hahn Y . Transcriptome analysis of human gastric cancer. . Mamm. Genome . 16 . 12 . 942–54 . 2006 . 16341674 . 10.1007/s00335-005-0075-2 . 69278 . etal.
• Twu KY, Kuo RL, Marklund J, Krug RM . The H5N1 influenza virus NS genes selected after 1998 enhance virus replication in mammalian cells. . J. Virol. . 81 . 15 . 8112–21 . 2007 . 17522219 . 10.1128/JVI.00006-07 . 1951328 .

Notes and References

1. Nemeroff ME, Barabino SM, Li Y, Keller W, Krug RM . 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 . Jul 1998 . 9651582 . 10.1016/S1097-2765(00)80099-4 . free .
2. 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 . 11 . 13 . 1703–16 . Aug 1997 . 9224719 . 10.1101/gad.11.13.1703 . free .
3. Web site: Entrez Gene: CPSF4 cleavage and polyadenylation specific factor 4, 30kDa.