| 2007 |
Crystal structure of the HAT (half a TPR) domain of murine CstF-77 revealed two subdomains (HAT-N and HAT-C) with drastically different helical orientations, forming a highly elongated homodimer spanning 165 Å mediated by the HAT-C domain. Light-scattering, yeast two-hybrid, and analytical ultracentrifugation confirmed this self-association, supporting a role for CstF dimerization in pre-mRNA 3' end processing. |
X-ray crystallography, light scattering, yeast two-hybrid, analytical ultracentrifugation |
Molecular cell |
High |
17386263
|
| 2007 |
Crystal structure of CstF-77 from Encephalitozoon cuniculi at 2 Å resolution revealed 11 Half-a-TPR repeats defining two domains and a tight homodimer exposing phylogenetically conserved surface areas for interaction with protein partners. Mapping experiments identified the C-terminal region of Rna14p (yeast CstF-77 homologue) as the docking domain for Rna15p (yeast CstF-64 homologue). |
X-ray crystallography, domain mapping experiments |
Nucleic acids research |
High |
17584787
|
| 2010 |
CstF-77 and symplekin bind mutually exclusively to the hinge domain of CstF-64. The nuclear accumulation of CstF-64 depends on its binding to CstF-77 (not symplekin), demonstrating that CstF-77 interaction is required for nuclear localization and maintenance of stoichiometric nuclear CstF complex levels. |
Mutant analysis (CstF-64 and symplekin mutants), nuclear localization assays, functional complementation |
Molecular biology of the cell |
High |
21119002
|
| 2009 |
The hinge domain of CstF-64 is essential for interaction with CstF-77 and consequent nuclear localization of CstF-64, demonstrating that nuclear import of a preformed CstF complex is an essential step in polyadenylation. |
In vivo SLAP (stem-loop luciferase assay for polyadenylation), domain deletion/mutation analysis, nuclear localization assays |
The Journal of biological chemistry |
High |
19887456
|
| 2018 |
The carboxy-terminus of CstF-77 (monkeytail-carboxy-terminal domain, last 30 amino acids) enhances cleavage/polyadenylation by increasing the stability of the RNA recognition motif (RRM) of CstF-64, thereby altering the affinity of the complex for RNA. CstF-64 relies on CstF-77 for nuclear transport; excess CstF-64 localizes to the cytoplasm, possibly via interaction with cytoplasmic RNAs. |
Reverse genetics, NMR spectroscopy of recombinant proteins (CstF-64 RRM-Hinge and CstF-77 monkeytail-CTD), nuclear localization assays |
Nucleic acids research |
High |
30257008
|
| 2002 |
Drosophila Su(f) (CstF-77 homologue) is required for pre-mRNA cleavage during mRNA 3' end formation in vivo. Chimeric human CstF-77/Su(f) proteins rescue lethality and cleavage defects in su(f) mutants, but a domain in human CstF-77 limiting for rescue is incapable of reproducing protein interactions with Drosophila CstF subunits. Chimeric proteins rescuing lethality cannot restore utilization of a regulated poly(A) site, indicating CstF-77 has an additional role in poly(A) site regulation. |
Genetic complementation in Drosophila su(f) mutants, chimeric protein rescue assays, mRNA 3' end processing analysis in vivo |
Proceedings of the National Academy of Sciences of the United States of America |
High |
12149458
|
| 2013 |
The CstF-77 gene contains a conserved intronic polyadenylation site (In3 pA) whose usage is responsive to CstF-77 expression levels and several other C/P factors, establishing a negative feedback autoregulatory mechanism. U1 snRNP inhibition also regulates In3 pA usage. Perturbation of CstF-77 expression leads to widespread alternative cleavage and polyadenylation (APA) and disturbance of cell proliferation and differentiation. |
Molecular biology validation of intronic poly(A) site, expression manipulation (overexpression/knockdown), U1 snRNP inhibition, global APA analysis |
PLoS genetics |
Medium |
23874216
|
| 2006 |
In Xenopus oocytes, CstF-77 (X77K) localizes mainly to the nucleus but also to punctate cytoplasmic foci, where it resides in a cytoplasmic complex with eIF4E, CPEB, CPSF-100, and XGLD2. X77K is not required for cytoplasmic polyadenylation per se, but impairment of X77K function accelerates the G2/M transition with premature synthesis of Mos and AuroraA proteins. X77K represses mRNA translation in vitro, suggesting a role in mRNA masking prior to polyadenylation. |
Co-immunoprecipitation, subcellular fractionation, in vivo function impairment (dominant negative/antibody injection), in vitro translation assay |
The Journal of biological chemistry |
Medium |
16882666
|
| 2024 |
CSTF3 directly binds downstream of the NEAT1 proximal polyadenylation site to promote usage of the proximal PAS, generating the short NEAT1_1 isoform. CSTF3 knockdown reduces proximal PAS usage, shifting expression toward the longer NEAT1_2 isoform and increasing platinum sensitivity in ovarian cancer cells. NEAT1_1 overexpression reverses platinum resistance after CSTF3 knockdown, and CSTF3/NEAT1_1 activity is linked to activation of the PI3K/AKT/mTOR pathway. |
CSTF3 knockdown in cell lines, RNA isoform analysis, lncRNA isoform-specific overexpression/knockdown, pathway activity measurement |
Cell death & disease |
Medium |
38898019
|
| 2026 |
α3β1 integrin-MEK/ERK signaling induces CSTF3 expression in keratinocytes to promote proximal polyadenylation site usage in the Mmp9 gene, generating a short, more stable Mmp9 mRNA. CSTF3 knockdown shifts Mmp9 toward distal PAS usage. α3 deletion reduced Cstf3 gene expression and altered APA genome-wide in vivo. |
Inducible epidermis-specific α3 knockout mice, RNA in situ hybridization, CSTF3 knockdown, DaPars2 genome-wide APA analysis |
Matrix biology : journal of the International Society for Matrix Biology |
Medium |
41628695
|
| 2005 |
Human and mouse CstF-77 genes contain an intronic polyadenylation site that produces short CstF-77 transcripts lacking sequences encoding domains involved in CstF-77 functions, analogous to the Drosophila su(f) intronic poly(A) site. The intronic poly(A) site is utilized across a wide range of tissues based on SAGE data validation. |
Bioinformatic identification with molecular biology experimental validation (RT-PCR, poly(A) site analysis), SAGE data analysis |
Gene |
Low |
16316725
|