Gene Symbol: CSTF2
Description: cleavage stimulation factor subunit 2
Alias: CstF-64, cleavage stimulation factor subunit 2, CF-1 64 kDa subunit, CSTF 64 kDa subunit, betaCstF-64 variant 2, cleavage stimulation factor 64 kDa subunit, cleavage stimulation factor, 3' pre-RNA, subunit 2, 64kD, cleavage stimulation factor, 3' pre-RNA, subunit 2, 64kDa
Species: human
Products:     CSTF2

Top Publications

  1. Takagaki Y, MacDonald C, Shenk T, Manley J. The human 64-kDa polyadenylylation factor contains a ribonucleoprotein-type RNA binding domain and unusual auxiliary motifs. Proc Natl Acad Sci U S A. 1992;89:1403-7 pubmed
  2. Hockert J, Yeh H, MacDonald C. The hinge domain of the cleavage stimulation factor protein CstF-64 is essential for CstF-77 interaction, nuclear localization, and polyadenylation. J Biol Chem. 2010;285:695-704 pubmed publisher
    ..Further, we showed that the Hinge domain is necessary for CstF-64 interaction with CstF-77 and consequent nuclear localization, suggesting that nuclear import of a preformed CstF complex is an essential step in polyadenylation. ..
  3. Kleiman F, Manley J. The BARD1-CstF-50 interaction links mRNA 3' end formation to DNA damage and tumor suppression. Cell. 2001;104:743-53 pubmed
    ..Together these results indicate a link between mRNA 3' processing and DNA repair and tumor suppression. ..
  4. Cevher M, Zhang X, Fernandez S, Kim S, Baquero J, Nilsson P, et al. Nuclear deadenylation/polyadenylation factors regulate 3' processing in response to DNA damage. EMBO J. 2010;29:1674-87 pubmed publisher
  5. Rozenblatt Rosen O, Nagaike T, FRANCIS J, Kaneko S, Glatt K, Hughes C, et al. The tumor suppressor Cdc73 functionally associates with CPSF and CstF 3' mRNA processing factors. Proc Natl Acad Sci U S A. 2009;106:755-60 pubmed publisher
    ..Our results suggest that Cdc73 facilitates association of 3' mRNA processing factors with actively-transcribed chromatin and support the importance of links between tumor suppression and mRNA maturation. ..
  6. Maciolek N, McNally M. Characterization of Rous sarcoma virus polyadenylation site use in vitro. Virology. 2008;374:468-76 pubmed publisher
  7. Takagaki Y, Seipelt R, Peterson M, Manley J. The polyadenylation factor CstF-64 regulates alternative processing of IgM heavy chain pre-mRNA during B cell differentiation. Cell. 1996;87:941-52 pubmed
    ..Our results indicate that CstF-64 plays a key role in regulating IgM heavy chain expression during B cell differentiation. ..
  8. Shell S, Hesse C, Morris S, Milcarek C. Elevated levels of the 64-kDa cleavage stimulatory factor (CstF-64) in lipopolysaccharide-stimulated macrophages influence gene expression and induce alternative poly(A) site selection. J Biol Chem. 2005;280:39950-61 pubmed
  9. Perez Canadillas J, Varani G. Recognition of GU-rich polyadenylation regulatory elements by human CstF-64 protein. EMBO J. 2003;22:2821-30 pubmed
    ..The structural distinction between sequences that form stable and unstable complexes provides an operational distinction between weakly and strongly processed poly(A) sites. ..

More Information


  1. Takagaki Y, Manley J. Complex protein interactions within the human polyadenylation machinery identify a novel component. Mol Cell Biol. 2000;20:1515-25 pubmed
    ..These and other data suggest that symplekin may function in assembly of the polyadenylation machinery. ..
  2. Dass B, McMahon K, Jenkins N, Gilbert D, Copeland N, MacDonald C. The gene for a variant form of the polyadenylation protein CstF-64 is on chromosome 19 and is expressed in pachytene spermatocytes in mice. J Biol Chem. 2001;276:8044-50 pubmed
    ..Features of mtauCstF-64 that might allow it to promote the germ cell pattern of polyadenylation include a Pro --> Ser substitution in the RNA-binding domain and significant changes in the region that interacts with CstF-77. ..
  3. Martincic K, Campbell R, Edwalds Gilbert G, Souan L, Lotze M, Milcarek C. Increase in the 64-kDa subunit of the polyadenylation/cleavage stimulatory factor during the G0 to S phase transition. Proc Natl Acad Sci U S A. 1998;95:11095-100 pubmed
    ..Because augmentation of CstF-64 levels is neither necessary nor sufficient for Ig secretory mRNA production, we conclude that other lymphokine-induced factors play a role. ..
  4. Takagaki Y, Manley J. Levels of polyadenylation factor CstF-64 control IgM heavy chain mRNA accumulation and other events associated with B cell differentiation. Mol Cell. 1998;2:761-71 pubmed
    ..Further reduction caused reversible cell cycle arrest in G0/G1 phase, while depletion resulted in apoptotic cell death. Our results indicate that CstF-64 plays unexpected roles in regulating gene expression and cell growth in B cells. ..
  5. Gharesouran J, Taheri M, Sayad A, Ghafouri Fard S, Mazdeh M, Omrani M. A Novel Regulatory Function of Long Non-coding RNAs at Different Levels of Gene Expression in Multiple Sclerosis. J Mol Neurosci. 2019;67:434-440 pubmed publisher
    ..Comparative Ct method via TaqMan assay was used to quantify transcript levels of MALAT1, HOTAIRM1, AGO2, CSTF2, CPSF7, and WDR33...
  6. Chen X, Zhang J, Luo J, Wu S, Yuan G, Ma N, et al. CSTF2-Induced Shortening of the RAC1 3'UTR Promotes the Pathogenesis of Urothelial Carcinoma of the Bladder. Cancer Res. 2018;78:5848-5862 pubmed publisher
    ..An important cleavage/polyadenylation factor, cleavage stimulation factor 2 (CSTF2), induced 3'UTR shortening of RAC1 in UCB by mediating slow transcriptional elongation at RAC1 ..
  7. Mitra M, Johnson E, Swamy V, Nersesian L, Corney D, Robinson D, et al. Alternative polyadenylation factors link cell cycle to migration. Genome Biol. 2018;19:176 pubmed publisher
    ..Our findings support cleavage and polyadenylation factors as a link between cellular proliferation state and migration. ..
  8. Youngblood B, MacDonald C. CstF-64 is necessary for endoderm differentiation resulting in cardiomyocyte defects. Stem Cell Res. 2014;13:413-21 pubmed publisher
    ..However, CstF-64 knockout (Cstf2(E6)) cells were able to differentiate into neuronal progenitors, demonstrating that some differentiation pathways ..
  9. Grozdanov P, MacDonald C. Generation of plasmid vectors expressing FLAG-tagged proteins under the regulation of human elongation factor-1α promoter using Gibson assembly. J Vis Exp. 2015;: pubmed publisher
    ..Initial screen of the plasmids was done by restriction digestion, followed by sequencing. In conclusion, GA allowed us to create customized plasmids for gene expression in 5 days, including construct screens and verification. ..
  10. Cao W, Ma E, Zhou L, Yuan T, Zhang C. Exploring the FGFR3-related oncogenic mechanism in bladder cancer using bioinformatics strategy. World J Surg Oncol. 2017;15:66 pubmed publisher
    ..Moreover, CSTF2, POLA1, HMOX2, and EFNB2 may be associated with the prognosis of bladder cancer patient...
  11. Harris J, Martinez J, Grozdanov P, Bergeson S, Grammas P, MacDonald C. The Cstf2t Polyadenylation Gene Plays a Sex-Specific Role in Learning Behaviors in Mice. PLoS ONE. 2016;11:e0165976 pubmed publisher
    ..CstF-64 (the 64,000 Mr subunit of the cleavage stimulation factor; gene symbol Cstf2) is an RNA-binding protein that regulates mRNA polyadenylation site usage...
  12. Akman H, Oyken M, Tuncer T, Can T, Erson Bensan A. 3'UTR shortening and EGF signaling: implications for breast cancer. Hum Mol Genet. 2015;24:6910-20 pubmed publisher
    ..To begin addressing the underlying mechanisms, we found CSTF2 (cleavage stimulation factor 2), a major regulator of 3'UTR shortening to be up-regulated in response to epidermal ..
  13. Tan S, Ding K, Chong Q, Zhao J, Liu Y, Shao Y, et al. Post-transcriptional regulation of ERBB2 by miR26a/b and HuR confers resistance to tamoxifen in estrogen receptor-positive breast cancer cells. J Biol Chem. 2017;292:13551-13564 pubmed publisher
    ..the HuR mRNA 3'-UTR via alternative polyadenylation (APA) was observed to be dependent on cleavage stimulation factor subunit 2 (CSTF2/CstF-64), which is up-regulated in the TAMR breast cancer cells...
  14. Grozdanov P, Amatullah A, Graber J, MacDonald C. TauCstF-64 Mediates Correct mRNA Polyadenylation and Splicing of Activator and Repressor Isoforms of the Cyclic AMP-Responsive Element Modulator (CREM) in Mouse Testis. Biol Reprod. 2016;94:34 pubmed publisher
  15. Ruepp M, Schweingruber C, Kleinschmidt N, Schumperli D. Interactions of CstF-64, CstF-77, and symplekin: implications on localisation and function. Mol Biol Cell. 2011;22:91-104 pubmed publisher
    ..Thus, the interactions between CstF-64/CstF-64Tau and CstF-77 are important for the maintenance of stoichiometric nuclear levels of the CstF complex components and for their intracellular localization, stability, and function. ..
  16. Nazim M, Masuda A, Rahman M, Nasrin F, Takeda J, Ohe K, et al. Competitive regulation of alternative splicing and alternative polyadenylation by hnRNP H and CstF64 determines acetylcholinesterase isoforms. Nucleic Acids Res. 2017;45:1455-1468 pubmed publisher
    ..We propose that hnRNP H is an essential factor that competitively regulates alternative splicing and alternative polyadenylation. ..
  17. Kleiman F, Manley J. Functional interaction of BRCA1-associated BARD1 with polyadenylation factor CstF-50. Science. 1999;285:1576-9 pubmed
  18. Yao C, Biesinger J, Wan J, Weng L, Xing Y, Xie X, et al. Transcriptome-wide analyses of CstF64-RNA interactions in global regulation of mRNA alternative polyadenylation. Proc Natl Acad Sci U S A. 2012;109:18773-8 pubmed publisher
    ..Taken together, our findings provide insight into the mechanisms of PAS recognition and identify CstF64 as an important global regulator of APA. ..
  19. Takagaki Y, Manley J. A polyadenylation factor subunit is the human homologue of the Drosophila suppressor of forked protein. Nature. 1994;372:471-4 pubmed
    ..Our results thus also indicate that components of the complex polyadenylation machinery are conserved from yeast to man. ..
  20. Kandala D, Mohan N, A V, A P S, G R, Laishram R. CstF-64 and 3'-UTR cis-element determine Star-PAP specificity for target mRNA selection by excluding PAPα. Nucleic Acids Res. 2016;44:811-23 pubmed publisher
    ..Our results suggest a mechanism of poly (A) site selection that has potential implication on the regulation of alternative polyadenylation. ..
  21. Romeo V, Griesbach E, Schümperli D. CstF64: cell cycle regulation and functional role in 3' end processing of replication-dependent histone mRNAs. Mol Cell Biol. 2014;34:4272-84 pubmed publisher
  22. Aragaki M, Takahashi K, Akiyama H, Tsuchiya E, Kondo S, Nakamura Y, et al. Characterization of a cleavage stimulation factor, 3' pre-RNA, subunit 2, 64 kDa (CSTF2) as a therapeutic target for lung cancer. Clin Cancer Res. 2011;17:5889-900 pubmed publisher
    ..In this process, we detected a gene encoding cleavage stimulation factor, 3' pre-RNA, subunit 2, 64 kDa (CSTF2) as a candidate...
  23. Takagaki Y, Manley J. A human polyadenylation factor is a G protein beta-subunit homologue. J Biol Chem. 1992;267:23471-4 pubmed
    ..Possible roles of the transducin repeat, both in CstF function specifically and in other beta-subunit homologues more generally, are discussed. ..
  24. Shankarling G, Coates P, Dass B, MacDonald C. A family of splice variants of CstF-64 expressed in vertebrate nervous systems. BMC Mol Biol. 2009;10:22 pubmed publisher
    ..We propose that betaCstF-64 contributes to proteomic diversity by regulating alternative polyadenylation of neural mRNAs. ..
  25. Rüegsegger U, Beyer K, Keller W. Purification and characterization of human cleavage factor Im involved in the 3' end processing of messenger RNA precursors. J Biol Chem. 1996;271:6107-13 pubmed
    ..Furthermore, the CstF-CPSF-RNA as well as the CstF-CPSF-PAP-RNA complex are supershifted and stabilized upon the addition of CF Im. ..
  26. Xing H, Mayhew C, Cullen K, Park Sarge O, Sarge K. HSF1 modulation of Hsp70 mRNA polyadenylation via interaction with symplekin. J Biol Chem. 2004;279:10551-5 pubmed
    ..Thus, HSF1 regulates HSP gene expression at not one but two different steps of the expression pathway, functioning both as a transcription factor and a polyadenylation stimulatory factor. ..
  27. Gonzales M, Mellman D, Anderson R. CKIalpha is associated with and phosphorylates star-PAP and is also required for expression of select star-PAP target messenger RNAs. J Biol Chem. 2008;283:12665-73 pubmed publisher
    ..The Star-PAP complex therefore represents a location where multiple signaling pathways converge to regulate the expression of specific mRNAs. ..
  28. Schul W, Groenhout B, Koberna K, Takagaki Y, Jenny A, Manders E, et al. The RNA 3' cleavage factors CstF 64 kDa and CPSF 100 kDa are concentrated in nuclear domains closely associated with coiled bodies and newly synthesized RNA. EMBO J. 1996;15:2883-92 pubmed
    ..the distribution of 3' cleavage factors in the nuclei of human T24 cells, monoclonal antibodies against the CstF 64 kDa subunit and against the CPSF 100 kDa subunit were used for immunofluorescent labelling...
  29. 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;23:616-26 pubmed
    ..These results show that hFip1 significantly contributes to CPSF-mediated stimulation of PAP activity. ..
  30. McCracken S, Fong N, Yankulov K, Ballantyne S, Pan G, Greenblatt J, et al. The C-terminal domain of RNA polymerase II couples mRNA processing to transcription. Nature. 1997;385:357-61 pubmed
  31. Calvo O, Manley J. Evolutionarily conserved interaction between CstF-64 and PC4 links transcription, polyadenylation, and termination. Mol Cell. 2001;7:1013-23 pubmed
    ..Our findings provide an additional, unexpected connection between transcription and polyadenylation and suggest that PC4/Sub1p, via its interaction with CstF-64/Rna15p, possesses an evolutionarily conserved antitermination activity. ..
  32. Laishram R, Anderson R. The poly A polymerase Star-PAP controls 3'-end cleavage by promoting CPSF interaction and specificity toward the pre-mRNA. EMBO J. 2010;29:4132-45 pubmed publisher
    ..The data support a model where Star-PAP binds to the RNA, recruits the CPSF complex to the 3'-end of pre-mRNA and then defines cleavage by CPSF 73 and subsequent polyadenylation of its target mRNAs. ..
  33. Bleoo S, Sun X, Hendzel M, Rowe J, Packer M, Godbout R. Association of human DEAD box protein DDX1 with a cleavage stimulation factor involved in 3'-end processing of pre-MRNA. Mol Biol Cell. 2001;12:3046-59 pubmed
    ..These studies are the first to identify a DEAD box protein associating with factors involved in 3'-end cleavage and polyadenylation of pre-mRNAs. ..
  34. Takagaki Y, Manley J. RNA recognition by the human polyadenylation factor CstF. Mol Cell Biol. 1997;17:3907-14 pubmed
    ..We discuss these results in terms of the function and evolution of mRNA 3'-end signals. ..
  35. Yang W, Hsu P, Yang F, Song J, Varani G. Reconstitution of the CstF complex unveils a regulatory role for CstF-50 in recognition of 3'-end processing signals. Nucleic Acids Res. 2017;: pubmed publisher
    ..We further demonstrate that CstF-77 boosts the affinity of the CstF-64 RRM to the RNA targets and CstF-50 fine tunes the ability of the complex to recognize G/U sequences of certain lengths and content...
  36. Deka P, Rajan P, Perez Canadillas J, Varani G. Protein and RNA dynamics play key roles in determining the specific recognition of GU-rich polyadenylation regulatory elements by human Cstf-64 protein. J Mol Biol. 2005;347:719-33 pubmed
    ..This behavior may be a general mechanism by which some RNA-binding proteins are able to bind to classes of sequences, as opposed to a well-defined sequence or consensus. ..
  37. Uhlmann T, Boeing S, Lehmbacher M, Meisterernst M. The VP16 activation domain establishes an active mediator lacking CDK8 in vivo. J Biol Chem. 2007;282:2163-73 pubmed
    ..We provide in vitro and in vivo evidence that VP16 activates transcription through a specific MED25-associated Mediator, which is deficient in CDK8. ..
  38. Murthy K, Manley J. The 160-kD subunit of human cleavage-polyadenylation specificity factor coordinates pre-mRNA 3'-end formation. Genes Dev. 1995;9:2672-83 pubmed
    ..We discuss the significance of these multiple functions and also a possible evolutionary link between yeast and mammalian polyadenylation suggested by the properties and sequence of 160K. ..
  39. Kolev N, Yario T, Benson E, Steitz J. Conserved motifs in both CPSF73 and CPSF100 are required to assemble the active endonuclease for histone mRNA 3'-end maturation. EMBO Rep. 2008;9:1013-8 pubmed publisher
    ..This indicates that CPSF73 and CPSF100 act together in the process of maturation of eukaryotic pre-messenger RNAs, similar to other members of the MBL family, RNases Z and J, which function as homodimers. ..
  40. Xia Z, Donehower L, Cooper T, Neilson J, Wheeler D, Wagner E, et al. Dynamic analyses of alternative polyadenylation from RNA-seq reveal a 3'-UTR landscape across seven tumour types. Nat Commun. 2014;5:5274 pubmed publisher
    ..Finally, our results implicate CstF64, an essential polyadenylation factor, as a master regulator of 3'-UTR shortening across multiple tumour types. ..
  41. Di Giammartino D, Li W, Ogami K, Yashinskie J, Hoque M, Tian B, et al. RBBP6 isoforms regulate the human polyadenylation machinery and modulate expression of mRNAs with AU-rich 3' UTRs. Genes Dev. 2014;28:2248-60 pubmed publisher
    ..Our results implicate RBBP6 and iso3 as novel regulators of 3' processing, especially of RNAs with AU-rich 3' UTRs. ..
  42. Yao C, Choi E, Weng L, Xie X, Wan J, Xing Y, et al. Overlapping and distinct functions of CstF64 and CstF64? in mammalian mRNA 3' processing. RNA. 2013;19:1781-90 pubmed publisher
    ..Together, our study of CstF64 and CstF64? revealed both functional overlap and specificity of these two important mRNA 3' processing factors and provided new insights into the regulatory mechanisms of mRNA 3' processing. ..