Alternative titles; symbols
HGNC Approved Gene Symbol: ZFP36L1
Cytogenetic location: 14q24.1 Genomic coordinates (GRCh38): 14:68,787,655-68,796,243 (from NCBI)
Bustin et al. (1994) cloned and characterized the ZFP36L1 gene, which they called ERF1, which is a member of the Tis11 family of early-response genes (see ZFP36; 190700). Members of this gene family contain a distinguishing putative zinc finger domain with a repeating cys-his motif and are induced by various agonists such as the phorbol ester TPA and the polypeptide mitogen EGF (131530). The human gene was cloned using a rat homolog as a probe. The rat and human genes have conserved 5-prime and 3-prime UTRs and their promoters contain motifs seen in other early-response genes. The predicted rat and human proteins are 99% identical.
Barnard et al. (1993) reported the coding sequence of ERF1. The ERF1 protein is 99% similar to the mouse Tis11b and rat Cmg1 proteins. It has a zinc finger motif similar to that of ZFP36.
Ning et al. (1996) also cloned ZFP36L1, which they termed BERG36. The deduced protein contains 338 amino acids.
Bustin et al. (1994) determined that the ZFP36L1 gene contains 2 exons and spans about 6 kb of genomic DNA including the promoter and UTRs.
Maclean et al. (1995) assigned the BRF1 gene to chromosome 14 with somatic cell hybrid DNAs and localized it to 14q22-q24 by fluorescence in situ hybridization.
Ning et al. (1996) found that BERG36 could be induced by treatment with calcium ionophore, and the induction could be blocked by treatment with interleukin-4 (IL4; 147780), but not by CD40 (109535) ligation. Treatment of the Epstein-Barr virus-negative human Burkitt lymphoma cell line Ramos, which phenotypically resembles germinal center B cells, with BERG36-antisense or with IL4 or CD40 ligation protected the cells from ionophore-induced apoptosis. CD40 ligation also protected Ramos cells from apoptosis induced by inhibitors of macromolecular synthesis. Ning et al. (1996) concluded that BERG36 is a target of IL4 signaling for B-cell survival.
Vignudelli et al. (2010) found that ZFP36L1 was expressed in all human hematopoietic lineages except the erythroid lineage. Overexpression of ZFP36L1 in human CD34 (142230)-positive cord blood-derived stem/progenitor cells inhibited their erythroid differentiation and colony formation, which appeared to be due to downregulation of STAT5B (604260) protein levels through degradation of STAT5B mRNA. Overexpression of ZFP36 (190700) also inhibited erythroid differentiation, and overexpression of both ZFP36 and ZFP36L1 had a cumulative effect. Both ZFP36 and ZFP36L1 directly bound a canonical AU-rich element II in the 3-prime UTR of STAT5B mRNA. Overexpression of ZFP36L1 also increased expression of IRF8 (601565), a transcription and proapoptotic factor expressed in myeloid and lymphoid lineages, but not in erythroid lineage. Vignudelli et al. (2010) concluded that ZFP36L1 negatively regulates erythroid differentiation by interfering with the STAT5B pathway in human hematopoietic stem cells.
Galloway et al. (2016) demonstrated in developing B lymphocytes, the RNA-binding proteins ZFP36L1 and ZFP36L2 (612053) are critical for maintaining quiescence before precursor B cell receptor (pre-BCR) expression and for reestablishing quiescence after pre-BCR-induced expansion. These RBPs suppress an evolutionarily conserved posttranscriptional regulon consisting of mRNAs whose protein products cooperatively promote transition in the S phase of the cell cycle. The mechanism promotes variable diversity joining (VDJ) recombination and effective selection of cells expressing immunoglobulin-mu (147020) at the pre-BCR checkpoint.
Stumpo et al. (2004) found that all Zfp36l1 knockout mouse embryos died in utero, most by about embryonic day 11. Failure of chorioallantoic fusion occurred in about two-thirds of cases. Even when fusion occurred, the affected placentas exhibited decreased cell division and relative atrophy of the trophoblast layers. Embryonic expression of Zfp36l1 at embryonic day 8.0 was greatest in the allantois, consistent with a role for Zfp36l1 in chorioallantoic fusion. Stumpo et al. (2004) concluded that lack of Zfp36l1 expression during midgestation results in abnormal stabilization of mRNAs whose encoded proteins cause abnormal placentation and fetal death.
Barnard, R. C., Pascall, J. C., Brown, K. D., McKay, I. A., Williams, N. S., Bustin, S. A. Coding sequence of ERF-1, the human homologue of Tis11b/cMG1, members of the Tis11 family of early response genes. Nucleic Acids Res. 21: 3580 only, 1993. [PubMed: 8346037] [Full Text: https://doi.org/10.1093/nar/21.15.3580]
Bustin, S. A., Nie, X.-F., Barnard, R. C., Kumar, V., Pascall, J. C., Brown, K. D., Leigh, I. M., Williams, N. S., McKay, I. A. Cloning and characterisation of ERF1, a human member of the Tis11 family of early-response genes. DNA Cell Biol. 13: 449-459, 1994. [PubMed: 8024689] [Full Text: https://doi.org/10.1089/dna.1994.13.449]
Galloway, A., Saveliev, A., Lukasiak, S., Hodson, D. J., Bolland, D., Balmanno, K., Ahlfors, H., Monzon-Casanova, E., Mannurita, S. C., Bell, L. S., Andrews, S., Diaz-Munoz, M. D., Cook, S. J., Corcoran, A., Turner, M. RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence. Science 352: 453-459, 2016. [PubMed: 27102483] [Full Text: https://doi.org/10.1126/science.aad5978]
Maclean, K. N., See, C. G., McKay, I. A., Bustin, S. A. The human immediate early gene BRF1 maps to chromosome 14q22-q24. Genomics 30: 89-90, 1995. [PubMed: 8595910] [Full Text: https://doi.org/10.1006/geno.1995.0014]
Ning, Z.-Q., Norton, J. D., Li, J., Murphy, J. J. Distinct mechanisms for rescue from apoptosis in Ramos human B cells by signaling through CD40 and interleukin-4 receptor: a role for inhibition of an early response gene, Berg36. Europ. J. Immun. 26: 2356-2363, 1996. [PubMed: 8898945] [Full Text: https://doi.org/10.1002/eji.1830261013]
Stumpo, D. J., Byrd, N. A., Phillips, R. S., Ghosh, S., Maronpot, R. R., Castranio, T., Meyers, E. N., Mishina, Y., Blackshear, P. J. Chorioallantoic fusion defects and embryonic lethality resulting from disruption of Zfp36L1, a gene encoding a CCCH tandem zinc finger protein of the tristetraprolin family. Molec. Cell. Biol. 24: 6445-6455, 2004. [PubMed: 15226444] [Full Text: https://doi.org/10.1128/MCB.24.14.6445-6455.2004]
Vignudelli, T., Selmi, T., Martello, A., Parenti, S., Grande, A., Gemelli, C., Zanocco-Marani, T., Ferrari, S. ZFP36L1 negatively regulates erythroid differentiation of CD34+ hematopoietic stem cells by interfering with the Stat5b pathway. Molec. Biol. Cell 21: 3340-3351, 2010. [PubMed: 20702587] [Full Text: https://doi.org/10.1091/mbc.E10-01-0040]