Alternative titles; symbols
HGNC Approved Gene Symbol: ZC3H7B
Cytogenetic location: 22q13.2 Genomic coordinates (GRCh38): 22:41,301,525-41,360,147 (from NCBI)
ZC3H7B is an RNA-binding protein that may be involved in translation regulation. ZC3H7B interacts with the rotavirus nonstructural protein NSP3 and may play a role in rotavirus replication (Vitour et al., 2004). ZC3H7B also appears to play a role in biogenesis of microRNAs (miRNAs) (Treiber et al., 2017).
By yeast 2-hybrid screening of a monkey kidney CV-1 cell cDNA library to identify proteins that interact with the rotavirus nonstructural protein NSP3, followed by database analysis, Vitour et al. (2004) identified human ZC3H7B, which they called ROXAN1. Human ROXAN1 contains 977 amino acids and has a calculated molecular mass of 110 kD. ROXAN1 has tetratricopeptide repeats (TPRs) and a leucine-aspartate (LD) protein-protein interaction motif in its N-terminal half, and 1 C2H2-type and 4 C3H1-type zinc finger motifs in its C-terminal half. ROXAN1 also has a C-terminal coiled-coil domain. Database analysis suggested that ROXAN1 mRNA is expressed ubiquitously. Database analysis identified clear orthologs of ROXAN1 in mammals, fish, amphibians, birds, and the invertebrate chordate sea squirt.
Vitour et al. (2004) stated that the ZC3H7B gene maps to chromosome 22.
Gross (2018) mapped the ZC3H7B gene to chromosome 22q13.2 based on an alignment of the ZC3H7B sequence (GenBank AF188530) with the genomic sequence (GRCh38).
By yeast 2-hybrid analysis, coimmunoprecipitation analysis in transfected COS-7 cells, and mutation analysis in transfected HEK293 cells, Vitour et al. (2004) showed that the LD motif of ROXAN1 interacted with amino acids 163 to 240 of NSP3 during rotavirus infection. The region of NSP3 required for interaction with ROXAN1 includes a portion of the NSP3 dimerization domain and is close to the eIF4G (EIF4G1; 600495)-binding domain. Yeast sandwich-hybrid assays and immunoprecipitation analysis in transfected COS-7 cells revealed that the NSP3 dimer could interact simultaneously with ROXAN1 and eIF4G to form a ternary complex in rotavirus-infected cells. In transfected HEK293 cells, ROXAN1 and eIF4G interacted only in the presence of NSP3. Vitour et al. (2004) hypothesized that ROXAN1 may play a role in translation regulation.
By modeling the NSP3-ROXAN complex, Harb et al. (2008) identified 2 mutations in NSP3, arg187 to glu (R187E) and lys191 to glu (K191E), that disrupted its interaction with ROXAN without affecting eIF4G binding. Using these mutations, the authors found that disruption of the NSP3-ROXAN interaction dramatically reduced the efficiency of nuclear localization of PABPC1 (604679), a nucleocytoplasmic shuttling protein. Coimmunoprecipitation analysis in transfected HEK293 cells showed that PABPC1 and ROXAN bound RNA with different sequence specificity and interacted with one another through an RNA intermediate. PABPC1 exits the nucleus using a CRM1 (XPO1; 602559)-dependent export pathway that relies on interaction of CRM1 with a nuclear export signal. Mutation analysis showed that the ROXAN LD domain could function as an NES in PABPC1 export. Immunofluorescence analysis demonstrated that ROXAN and PABC1 localized mainly to nuclei and cytoplasm, respectively, in uninfected cells, whereas nuclei of rotavirus-infected cells accumulated PABPC1 and were depleted of ROXAN. Harb et al. (2008) concluded that ROXAN is a cellular partner of NSP3 involved in nucleocytoplasmic localization of PABC1.
Using a proteomics-based pull-down approach, Treiber et al. (2017) found that human ZC3H7B and its paralog, ZC3H7A (619819), interacted with the hairpins of the MIR7-1 (615239), MIR16-2, and MIR29A (610782) precursors. Further analysis showed that the ZC3H7 proteins recognized ATA(A/T) motifs in the apical loops of the hairpins. Knockout of ZC3H7B in HEK293 cells reduced mature MIR7 levels. Knockout of both ZC3H7A and ZC3H7B in HEK293 cells confirmed that the proteins functioned redundantly in regulating MIR7-1 biogenesis.
Gross, M. B. Personal Communication. Baltimore, Md. 11/28/2018.
Harb, M., Becker, M. M., Vitour, D., Baron, C. H., Vende, P., Brown, S. C., Bolte, S., Arold, S. T., Poncet, D. Nuclear localization of cytoplasmic poly(A)-binding protein upon rotavirus infection involves the interaction of NSP3 with eIF4G and RoXaN. J. Virol. 82: 11283-11293, 2008. [PubMed: 18799579] [Full Text: https://doi.org/10.1128/JVI.00872-08]
Treiber, T., Treiber, N., Plessmann, U., Harlander, S., Daiss, J.-L., Eichner, N., Lehmann, G., Schall, K., Urlaub, H., Meister, G. A compendium of RNA-binding proteins that regulate microRNA biogenesis. Molec. Cell 66: 270-284, 2017. [PubMed: 28431233] [Full Text: https://doi.org/10.1016/j.molcel.2017.03.014]
Vitour, D., Lindenbaum, P., Vende, P., Becker, M. M., Poncet, D. RoXaN, a novel cellular protein containing TPR, LD, and zinc finger motifs, forms a ternary complex with eukaryotic initiation factor 4G and rotavirus NSP3. J. Virol. 78: 3851-3862, 2004. [PubMed: 15047801] [Full Text: https://doi.org/10.1128/jvi.78.8.3851-3862.2004]