CSTF2

CSTF2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1P1T, 2J8P
Identifiers
Aliases	CSTF2, CstF-64, cleavage stimulation factor subunit 2
External IDs	OMIM: 300907; MGI: 1343054; HomoloGene: 80171; GeneCards: CSTF2; OMA:CSTF2 - orthologs
Gene location (Human) Chr. X chromosome (human)[1] Band Xq22.1 Start 100,820,359 bp[1] End 100,841,520 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X|X E3 Start 132,959,936 bp[2] End 132,987,568 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in oocyte secondary oocyte oral cavity gonad palpebral conjunctiva mucosa of pharynx testicle ganglionic eminence buccal mucosa cell epithelium of nasopharynx Top expressed in ventromedial nucleus dorsomedial hypothalamic nucleus paraventricular nucleus of hypothalamus lateral hypothalamus lateral septal nucleus dorsal tegmental nucleus anterior amygdaloid area ventral tegmental area arcuate nucleus subiculum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleic acid binding protein binding mRNA binding RNA binding Cellular component mRNA cleavage and polyadenylation specificity factor complex cleavage body nucleoplasm nucleus nuclear body Biological process mRNA splicing, via spliceosome termination of RNA polymerase II transcription mRNA processing mRNA 3'-end processing pre-mRNA cleavage required for polyadenylation tRNA splicing, via endonucleolytic cleavage and ligation mRNA polyadenylation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1478 108062 Ensembl ENSG00000101811 ENSMUSG00000031256 UniProt P33240 Q8BIQ5 RefSeq (mRNA) NM_001306206 NM_001306209 NM_001325 NM_001290398 NM_001290399 NM_133196 NM_001359053 NM_001359054 RefSeq (protein) NP_001293135 NP_001293138 NP_001316 NP_001293135.1 NP_001277327 NP_001277328 NP_573459 NP_001345982 NP_001345983 Location (UCSC) Chr X: 100.82 – 100.84 Mb Chr X: 132.96 – 132.99 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Cleavage stimulation factor 64 kDa subunit is a protein that in humans is encoded by the CSTF2 gene,which is located on the X-chromosome in Homo sapiens, but has an autosomal paralog CSTF2T on chromosome 19 coding for the protein CstF64τ.^[5]

This gene encodes a nuclear protein with an RRM (RNA recognition motif) domain. The protein is a member of the cleavage stimulation factor (CSTF) complex that is involved in the 3' end cleavage and polyadenylation of pre-mRNAs. Specifically, this protein binds GU-rich elements within the 3'-untranslated region of mRNAs.^[6][7]ition motif) domain. The protein is a member of the cleavage stimulation factor (CSTF) complex that is involved in the 3' end cleavage and polyadenylation of pre-mRNAs. Specifically, this protein binds GU-rich elements within the 3'-untranslated region of mRNAs.

This gene encodes a nuclear protein with an RRM (RNA recognition motif) domain. The protein is a member of the cleavage stimulation factor (CSTF) complex that is involved in the 3' end cleavage and polyadenylation of pre-mRNAs. Specifically, this protein binds GU-rich elements within the 3'-untranslated region of mRNAs.^[7]

Tissue distribution

CSTF2 has broad distribution across human tissues, with generally higher mRNA and protein levels in hematopoietic/immune tissues, reproductive organs, and many epithelial organs. It is detectable in essentially all sampled normal tissues, but is particularly enriched in testis, ovary, and various mucosal/secretory epithelia (e.g., oral cavity, gastrointestinal tract). CSTF2 expression is also observed in subsets of brain and immune cells. Across tumors, CSTF2 expression is frequently elevated relative to matched normal tissues in multiple cancer types, consistent with enrichment in highly proliferative cell populations.^[8][9]

Testes

Cleavage stimulation factor 2 is encoded by an X-chromosomal gene and is transcriptionally silenced during male meiosis due to X-chromosome inactivation. As a result, CSTF2 is not expressed in mammalian testes. Instead, its autosomal paralog, CSTF2T (also known as CSTF-64τ), is specifically expressed in testes and serves as the predominant CSTF2 family member in this tissue.^[10]

Central nervous system

Multiple CSTF2 family isoforms are expressed in the mammalian nervous system, including CSTF-64, CSTF-64τ, and βCSTF-64. βCSTF-64 is broadly expressed across all regions of the brain and in peripheral nerves in vertebrates. Minor levels of CSTF-64τ are also detectable in immune cells.^[11][12]

Immune system

CSTF2 is expressed in immune cells, including B lymphocytes, where its abundance varies with differentiation state and activation status. Minor expression of CSTF-64τ has also been reported in immune cell populations.^[11]

Structure

The CSTF2 mRNA is roughly 2000 base pairs long when isolated from HeLa cells, excluding the polyadenylated region.^[6] In the translated protein, the RNA recognition motif (RRM) is composed of multiple β-sheets and is located at the N-terminus of the protein.^[13] This domain recognizes guanine and uracil bases.

In addition to the RRM, CSTF2 contains a hinge domain and a C-terminal domain. The hinge domain consists of approximately 40–50 amino acid residues and mediates binding to the cleavage specificity factor subunit symplekin. The C-terminal domain remains comparatively under-researched; however, when the cleavage specificity factor complex is bound to cleavage stimulation factor 3 and associated with the rest of the cleavage stimulation factor complex through the hinge domain of CSTF2, the assembled complexes are transported into the nucleus.^{[14][failed verification]}

Human CSTF2 and CSTF3 share strong homology with corresponding proteins in yeast and Drosophila, indicating evolutionary conservation of both structure and function. Notably, the cleavage stimulation factor 3 subunit in Homo sapiens is highly similar to a Drosophila modifier gene, suggesting conserved roles in gene regulation and vertebrate cell growth.^[6][15]

Function

Cleavage stimulation factor 2 (CSTF2 or CSTF-64) is one of three subunits that assemble with cleavage stimulation factor 1 (55 kDa) and cleavage stimulation factor 3 (77 kDa) to form the heterotrimeric cleavage stimulation factor (CSTF) complex. CSTF is an essential component of mRNA maturation due to its regulatory role in pre-mRNA cleavage and polyadenylation. When assembled, cleavage stimulation factor 2 binds pre-mRNA near the 3′ end of the transcript, recognizing G/U-rich sequence elements downstream of the cleavage site through its ribonucleoprotein-type RNA binding domain.^[16][17] This interaction helps define cleavage site selection and enables recruitment of additional processing machinery.

Cleavage and polyadenylation require coordinated binding of multiple complexes on both sides of the cleavage site. The cleavage specificity factor complex—comprising CPSF-160, CPSF-100, CPSF-73, CPSF-30, FIP1, and WDR33—binds upstream, while CSTF binds downstream. Together, these complexes regulate cleavage efficiency and contribute to determining poly(A) tail length. All three CSTF subunits must be assembled for cleavage and polyadenylation to occur, and CSTF acts as the primary regulatory unit of the process. Without cleavage stimulation factor 2 bound to the U/G-rich RNA sequence, neither cleavage nor polyadenylation occurs, even though CSTF does not directly cleave RNA. This requirement applies to both constitutive and alternative cleavage and polyadenylation events.^[11][16] Additionally, the C-terminal domain of cleavage stimulation factor 3 modulates RNA recognition by the RRM of cleavage stimulation factor 2 without directly contacting the RNA-binding domain.^[16]

Cleavage stimulation factor 2, and potentially cleavage stimulation factor 3, also participate in histone pre-mRNA processing through the heat-labile factor (HLF). CSTF2 is regulated by the cell cycle, and depletion of CSTF2 slows progression through the S-phase.^[18] This effect results from impaired pre-mRNA cleavage and maturation, which inhibits transcriptional completion. Histone RNA processing, including cleavage and maturation of non-polyadenylated RNA, is similarly dependent on CSTF2 levels during the transition from the G1 phase to the S phase.^[18]

Cleavage stimulation factor 2 is also essential for regulated gene expression. In its absence, cleavage stimulation factors 1 and 3 cannot independently regulate gene expression due to unstable association with pre-mRNA. When CSTF2 is present, gene expression increases substantially, largely through enhanced recruitment and activity of cleavage stimulation factor 3.^[16] The RNA recognition motif of CSTF2 performs two functions: recognition of the U/G-rich downstream sequence element and association with cleavage stimulation factor 3 to regulate localization of the CSTF complex between the nucleus and cytoplasm. The RRM of CSTF2, as well as its bacterial counterpart Rna15, does not bind a strict consensus sequence but instead interacts with U/G-rich regions through resonance structure–dependent binding mechanisms.^[19]

CSTF2 functions as a core component of the cleavage stimulation factor (CstF) complex, which regulates cleavage and polyadenylation of pre-mRNA 3′ ends. Through modulation of polyadenylation site selection, CSTF2 influences transcript stability, localization, and translational efficiency, particularly in rapidly dividing or highly differentiated cells.

Spermatogenesis

In mammals, CSTF2T (CSTF-64τ) functionally replaces CSTF2 during spermatogenesis. Mouse models lacking CSTF-64τ show severe defects in spermatogenesis, indicating that CSTF2 family proteins are essential for proper germ cell development. Although CSTF2 and CSTF-64τ regulate a relatively limited set of target genes, loss of either significantly reduces expression of spermatogenesis-associated transcripts, leading to impaired testicular development and infertility.^[10]

Nervous system polyadenylation

The βCSTF-64 isoform contains an additional 49 amino acids within the proline/glycine-rich domain and is generated by inclusion of nervous-system-specific exons from the CSTF2 gene. βCSTF-64 differs functionally from canonical CSTF-64 in its response to polyadenylation signal strength, showing reduced sensitivity to strong polyadenylation sites. This property enables fine regulation of alternative polyadenylation in neurons and contributes to nervous-system-specific transcript diversity.^[12]

Immunoglobulin class switching

In B cells, CSTF2 levels directly influence immunoglobulin heavy-chain mRNA processing. CSTF2 regulates the choice between upstream and downstream cleavage and polyadenylation sites, thereby determining whether immunoglobulin transcripts encode secreted or membrane-bound antibody forms. Increased CSTF2 favors usage of upstream polyadenylation sites, promoting production of secreted immunoglobulins, whereas lower CSTF2 levels favor membrane-bound forms.^[20]

Overlap between CSTF-64 and CSTF-64τ

Cleavage stimulation factor 2(CSTF-64) has its paralog CSTF-64τ that is capable of identifying a cleavage site for alternative polyadenylation.^[13][5] There is overlap between both the general CSTF-64 transcription factor and its alternative. In alternative polyadenylation, the utility of affected proteins are changed because of the alteration to the mRNA sequence. CSTF-64τ also consists of a N-terminal, a C-terminal, a RNA recognition motif, a hinge domain, and a P/G rich domain.^[21] Cleavage stimulation factor 2 and CSTF-64τ differ in their affinity for binding to the symplekin protein complex involved in polyadenylation. Symplekin protein complex is a scaffolding nuclear protein required for recruiting other polyadenylation machinery to the cleavage site.^[22] Cleavage stimulation factor 2 binds with more affinity to the symplekin complex than CSTF-64τ. This difference in binding affinity is due to size and presence of the P/G rich domain present in the CSTF-64τ variant that block the hinge domain from binding to the symplekin complex.^[13] Both protein variants bind to U/G rich sequence elements downstream of the cleavage site and play important roles in regulating the identification of cleavage and polyadenylation.^[21] But both variations will negatively regulate each other.^[13][14]

If cleavage stimulation factor 2 in its original form is present in the nucleus, then it will bind to the rest of the cleavage stimulation factor complex and the U/G rich region. Though in instances of cleavage stimulation factor 2 absence, if CSTF-64τ is present, then it will bind instead.^[16]  Both paralogs are redundant in their ability to bind both the rest of the cleavage stimulation factor complex, and to the RNA sequence itself. CSTF-64τ can also regulate alternative cleavage and polyadenylation in the same manner that its original can.  However, if both CSTF-64τ and cleavage stimulation factor 2 are depleted in the cell then the rate of cleavage and polyadenylation will decrease exponentially.^[21]

Regulation of alternative polyadenylation

Alternative polyadenylation is caused by the presence of one or more Poly A signal sequence. The polyadenylation site will have a stronger effect on gene expression if its affinity for binding transcription factors like cleavage specificity factor complex and cleavage stimulation factor complex.^[23] Polyadenylation and cleavage sites are determined in part by both the cleavage specificity factor complex and cleavage stimulation factor 2, which targets proximal potential sites containing the U/G rich region capable of binding to its RNA recognition motif.^[23] If both cleavage stimulation factor 2 and its CSFT-64τ variant are depleted, then there is a stronger selection for distal polyadenylation sites.^[24][25]

The subsequent alternative polyadenylation then causes lengthening or shortening of mature mRNA sequences that alter sequence elements like 3' untranslated regions(UTR). The variation of alternative polyadenylation has been linked to markers in certain stages of human cancers and other diseases.^[23] Specifically in colon cancer tissues, cleavage specificity factor 3 and cleavage stimulation factor 2 are expressed at a higher frequency than usual. 4 other cleavage and polyadenylation factors were over expressed in cancerous tissue as well, which differed from the normal regulation of alternative polyadenylation factor gene expression. The exact relation of these post-transcriptional factors to oncogenesis is not yet characterized.^[26]

Interactions

CSTF2 has been shown to interact with CSTF3,^[27] SUB1,^[28] SYMPK,^[27] BARD1^[29][30] and BRCA1.^[29][30]

References

1. GRCh38: Ensembl release 89: ENSG00000101811 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031256 – 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. Dass B, McMahon KW, Jenkins NA, Gilbert DJ, Copeland NG, MacDonald CC (March 2001). "The gene for a variant form of the polyadenylation protein CstF-64 is on chromosome 19 and is expressed in pachytene spermatocytes in mice". The Journal of Biological Chemistry. 276 (11): 8044–8050. doi:10.1074/jbc.M009091200. PMID 11113135.
6. Takagaki Y, MacDonald CC, Shenk T, Manley JL (February 1992). "The human 64-kDa polyadenylylation factor contains a ribonucleoprotein-type RNA binding domain and unusual auxiliary motifs". Proceedings of the National Academy of Sciences of the United States of America. 89 (4): 1403–1407. Bibcode:1992PNAS...89.1403T. doi:10.1073/pnas.89.4.1403. PMC 48459. PMID 1741396.
7. "Entrez Gene: CSTF2 cleavage stimulation factor, 3' pre-RNA, subunit 2, 64kDa".
8. Ding J, Su Y, Liu Y, Xu Y, Yang D, Wang X, et al. (2023). "The role of CSTF2 in cancer: from technology to clinical application". Cell Cycle. 22 (23–24). Georgetown, Texas: 2622–2636. doi:10.1080/15384101.2023.2299624. PMC 10936678. PMID 38166492.
9. Feng L, Jing F, Qin X, Zhou L, Ning Y, Hou J, et al. (2022). "Cleavage Stimulation Factor Subunit 2: Function Across Cancers and Potential Target for Chemotherapeutic Drugs". Frontiers in Pharmacology. 13 852469. doi:10.3389/fphar.2022.852469. PMC 8971630. PMID 35370655.
10. Dass B, Tardif S, Park JY, Tian B, Weitlauf HM, Hess RA, et al. (December 2007). "Loss of polyadenylation protein tauCstF-64 causes spermatogenic defects and male infertility". Proceedings of the National Academy of Sciences of the United States of America. 104 (51): 20374–20379. Bibcode:2007PNAS..10420374D. doi:10.1073/pnas.0707589104. PMC 2154438. PMID 18077340.
11. MacDonald CC (July 2019). "Tissue-specific mechanisms of alternative polyadenylation: Testis, brain, and beyond (2018 update)". Wiley Interdisciplinary Reviews. RNA. 10 (4) e1526. doi:10.1002/wrna.1526. PMC 6617714. PMID 30816016.
12. Shankarling GS, MacDonald CC (October 2013). "Polyadenylation site-specific differences in the activity of the neuronal βCstF-64 protein in PC-12 cells". Gene. 529 (2): 220–227. doi:10.1016/j.gene.2013.08.007. PMC 3783208. PMID 23948079.
13. Yao C, Choi EA, Weng L, Xie X, Wan J, Xing Y, et al. (December 2013). "Overlapping and distinct functions of CstF64 and CstF64τ in mammalian mRNA 3' processing". RNA. 19 (12): 1781–1790. doi:10.1261/rna.042317.113. PMC 3884657. PMID 24149845.
14. Hockert JA, Yeh HJ, MacDonald CC (January 2010). "The hinge domain of the cleavage stimulation factor protein CstF-64 is essential for CstF-77 interaction, nuclear localization, and polyadenylation". The Journal of Biological Chemistry. 285 (1): 695–704. doi:10.1074/jbc.M109.061705. PMC 2804217. PMID 19887456.
15. Takagaki Y, Manley JL (December 1998). "Levels of polyadenylation factor CstF-64 control IgM heavy chain mRNA accumulation and other events associated with B cell differentiation". Molecular Cell. 2 (6): 761–771. doi:10.1016/S1097-2765(00)80291-9. PMID 9885564.
16. Grozdanov PN, Masoumzadeh E, Latham MP, MacDonald CC (December 2018). "The structural basis of CstF-77 modulation of cleavage and polyadenylation through stimulation of CstF-64 activity". Nucleic Acids Research. 46 (22): 12022–12039. doi:10.1093/nar/gky862. PMC 6294498. PMID 30257008.
17. Mitschka S, Fansler MM, Mayr C (2021). Generation of 3'UTR knockout cell lines by CRISPR/Cas9-mediated genome editing. Methods in Enzymology. Vol. 655. pp. 427–457. doi:10.1016/bs.mie.2021.03.014. ISBN 978-0-12-823573-7. PMID 34183132.
18. Romeo V, Griesbach E, Schümperli D (December 2014). "CstF64: cell cycle regulation and functional role in 3' end processing of replication-dependent histone mRNAs". Molecular and Cellular Biology. 34 (23): 4272–4284. doi:10.1128/MCB.00791-14. PMC 4248742. PMID 25266659.
19. Pancevac C, Goldstone DC, Ramos A, Taylor IA (May 2010). "Structure of the Rna15 RRM-RNA complex reveals the molecular basis of GU specificity in transcriptional 3'-end processing factors". Nucleic Acids Research. 38 (9): 3119–3132. doi:10.1093/nar/gkq002. PMC 2875009. PMID 20097654.
20. Takagaki Y, Seipelt RL, Peterson ML, Manley JL (November 1996). "The polyadenylation factor CstF-64 regulates alternative processing of IgM heavy chain pre-mRNA during B cell differentiation". Cell. 87 (5): 941–952. doi:10.1016/S0092-8674(00)82000-0. PMID 8945520.
21. Yao C, Biesinger J, Wan J, Weng L, Xing Y, Xie X, et al. (November 2012). "Transcriptome-wide analyses of CstF64-RNA interactions in global regulation of mRNA alternative polyadenylation". Proceedings of the National Academy of Sciences of the United States of America. 109 (46): 18773–18778. Bibcode:2012PNAS..10918773Y. doi:10.1073/pnas.1211101109. PMC 3503179. PMID 23112178.
22. Xing H, Mayhew CN, Cullen KE, Park-Sarge OK, Sarge KD (March 2004). "HSF1 modulation of Hsp70 mRNA polyadenylation via interaction with symplekin". The Journal of Biological Chemistry. 279 (11): 10551–10555. doi:10.1074/jbc.M311719200. PMID 14707147.
23. Nourse J, Spada S, Danckwardt S (June 2020). "Emerging Roles of RNA 3'-end Cleavage and Polyadenylation in Pathogenesis, Diagnosis and Therapy of Human Disorders". Biomolecules. 10 (6): 915. doi:10.3390/biom10060915. PMC 7356254. PMID 32560344.
24. Li W, You B, Hoque M, Zheng D, Luo W, Ji Z, et al. (April 2015). "Systematic profiling of poly(A)+ transcripts modulated by core 3' end processing and splicing factors reveals regulatory rules of alternative cleavage and polyadenylation". PLOS Genetics. 11 (4) e1005166. doi:10.1371/journal.pgen.1005166. PMC 4407891. PMID 25906188.
25. Gruber AR, Martin G, Keller W, Zavolan M (December 2012). "Cleavage factor Im is a key regulator of 3' UTR length". RNA Biology. 9 (12): 1405–1412. doi:10.4161/rna.22570. PMID 23187700.
26. Mao Z, Zhao H, Qin Y, Wei J, Sun J, Zhang W, et al. (2020). "Post-Transcriptional Dysregulation of microRNA and Alternative Polyadenylation in Colorectal Cancer". Frontiers in Genetics. 11 64. doi:10.3389/fgene.2020.00064. PMC 7047281. PMID 32153636.
27. Takagaki Y, Manley JL (March 2000). "Complex protein interactions within the human polyadenylation machinery identify a novel component". Molecular and Cellular Biology. 20 (5): 1515–1525. doi:10.1128/MCB.20.5.1515-1525.2000. PMC 85326. PMID 10669729.
28. Calvo O, Manley JL (May 2001). "Evolutionarily conserved interaction between CstF-64 and PC4 links transcription, polyadenylation, and termination". Molecular Cell. 7 (5): 1013–1023. doi:10.1016/S1097-2765(01)00236-2. PMID 11389848.
29. Kleiman FE, Manley JL (March 2001). "The BARD1-CstF-50 interaction links mRNA 3' end formation to DNA damage and tumor suppression". Cell. 104 (5): 743–753. doi:10.1016/S0092-8674(01)00270-7. PMID 11257228.
30. Kleiman FE, Manley JL (September 1999). "Functional interaction of BRCA1-associated BARD1 with polyadenylation factor CstF-50". Science. 285 (5433): 1576–1579. doi:10.1126/science.285.5433.1576. PMID 10477523.

External links

• Human CSTF2 genome location and CSTF2 gene details page in the UCSC Genome Browser.

Further reading

• Takagaki Y, Manley JL (November 1992). "A human polyadenylation factor is a G protein beta-subunit homologue". The Journal of Biological Chemistry. 267 (33): 23471–23474. doi:10.1016/S0021-9258(18)35861-7. PMID 1358884.
• Murthy KG, Manley JL (November 1995). "The 160-kD subunit of human cleavage-polyadenylation specificity factor coordinates pre-mRNA 3'-end formation". Genes & Development. 9 (21): 2672–2683. doi:10.1101/gad.9.21.2672. PMID 7590244.
• Takagaki Y, Manley JL (December 1994). "A polyadenylation factor subunit is the human homologue of the Drosophila suppressor of forked protein". Nature. 372 (6505): 471–474. Bibcode:1994Natur.372..471T. doi:10.1038/372471a0. PMID 7984242. S2CID 4329672.
• Rüegsegger U, Beyer K, Keller W (March 1996). "Purification and characterization of human cleavage factor Im involved in the 3' end processing of messenger RNA precursors". The Journal of Biological Chemistry. 271 (11): 6107–6113. doi:10.1074/jbc.271.11.6107. PMID 8626397.
• Schul W, Groenhout B, Koberna K, Takagaki Y, Jenny A, Manders EM, et al. (June 1996). "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". The EMBO Journal. 15 (11): 2883–2892. doi:10.1002/j.1460-2075.1996.tb00649.x. PMC 450226. PMID 8654386.
• Takagaki Y, Seipelt RL, Peterson ML, Manley JL (November 1996). "The polyadenylation factor CstF-64 regulates alternative processing of IgM heavy chain pre-mRNA during B cell differentiation". Cell. 87 (5): 941–952. doi:10.1016/S0092-8674(00)82000-0. PMID 8945520.
• Takagaki Y, Manley JL (July 1997). "RNA recognition by the human polyadenylation factor CstF". Molecular and Cellular Biology. 17 (7): 3907–3914. doi:10.1128/MCB.17.7.3907. PMC 232243. PMID 9199325.
• Martincic K, Campbell R, Edwalds-Gilbert G, Souan L, Lotze MT, Milcarek C (September 1998). "Increase in the 64-kDa subunit of the polyadenylation/cleavage stimulatory factor during the G0 to S phase transition". Proceedings of the National Academy of Sciences of the United States of America. 95 (19): 11095–11100. Bibcode:1998PNAS...9511095M. doi:10.1073/pnas.95.19.11095. PMC 21601. PMID 9736695.
• Takagaki Y, Manley JL (December 1998). "Levels of polyadenylation factor CstF-64 control IgM heavy chain mRNA accumulation and other events associated with B cell differentiation". Molecular Cell. 2 (6): 761–771. doi:10.1016/S1097-2765(00)80291-9. PMID 9885564.
• Kleiman FE, Manley JL (September 1999). "Functional interaction of BRCA1-associated BARD1 with polyadenylation factor CstF-50". Science. 285 (5433): 1576–1579. doi:10.1126/science.285.5433.1576. PMID 10477523.
• Takagaki Y, Manley JL (March 2000). "Complex protein interactions within the human polyadenylation machinery identify a novel component". Molecular and Cellular Biology. 20 (5): 1515–1525. doi:10.1128/MCB.20.5.1515-1525.2000. PMC 85326. PMID 10669729.
• Dass B, McMahon KW, Jenkins NA, Gilbert DJ, Copeland NG, MacDonald CC (March 2001). "The gene for a variant form of the polyadenylation protein CstF-64 is on chromosome 19 and is expressed in pachytene spermatocytes in mice". The Journal of Biological Chemistry. 276 (11): 8044–8050. doi:10.1074/jbc.M009091200. PMID 11113135.
• Kleiman FE, Manley JL (March 2001). "The BARD1-CstF-50 interaction links mRNA 3' end formation to DNA damage and tumor suppression". Cell. 104 (5): 743–753. doi:10.1016/S0092-8674(01)00270-7. PMID 11257228.
• Calvo O, Manley JL (May 2001). "Evolutionarily conserved interaction between CstF-64 and PC4 links transcription, polyadenylation, and termination". Molecular Cell. 7 (5): 1013–1023. doi:10.1016/S1097-2765(01)00236-2. PMID 11389848.
• Bléoo S, Sun X, Hendzel MJ, Rowe JM, Packer M, Godbout R (October 2001). "Association of human DEAD box protein DDX1 with a cleavage stimulation factor involved in 3'-end processing of pre-MRNA". Molecular Biology of the Cell. 12 (10): 3046–3059. doi:10.1091/mbc.12.10.3046. PMC 60154. PMID 11598190.
• Pérez Cañadillas JM, Varani G (June 2003). "Recognition of GU-rich polyadenylation regulatory elements by human CstF-64 protein". The EMBO Journal. 22 (11): 2821–2830. doi:10.1093/emboj/cdg259. PMC 156756. PMID 12773396.
• Xing H, Mayhew CN, Cullen KE, Park-Sarge OK, Sarge KD (March 2004). "HSF1 modulation of Hsp70 mRNA polyadenylation via interaction with symplekin". The Journal of Biological Chemistry. 279 (11): 10551–10555. doi:10.1074/jbc.M311719200. PMID 14707147.