Xenopus ZFP36L1 (zinc finger protein 36, C3H type-like 1) belongs to the ZFP36 family of RNA-binding proteins, which contains two characteristic tandem CCCH-type zinc-finger domains. The ZFP36 proteins can bind AU-rich elements in 3' untranslated regions of target mRNAs and promote their turnover. However, the expression and role of ZFP36 genes during neural development in Xenopus embryos remains largely unknown. The present study showed that Xenopus ZFP36L1 was expressed at the dorsal part of the forebrain, forebrain-midbrain boundary, and midbrain-hindbrain boundary from late neurula stages to tadpole stages of embryonic development. Overexpression of XZFP36L1 in Xenopus embryos inhibited neural induction and differentiation, leading to severe neural tube defects. The function of XZP36L1 requires both its zinc finger and C terminal domains, which also affect its subcellular localization. These results suggest that XZFP36L1 is likely involved in neural development in Xenopus and might play an important role in post-transcriptional regulation.Keywords: ZFP36L1; RNA-binding protein; Neural development; Xenopus; Post-transcriptional regulation mRNA stability is an important mechanism for gene expression regulation, which is critical for embryogenesis and normal physiological processes. The zinc finger protein 36 (ZFP36) family proteins are key players in post-transcriptional regulation and contain two or more highly conserved tandem CCCH zinc fingers (TZF) of tandem Cx8Cx5Cx3H repeats (x represents a variable amino acid). These factors are able to bind to AU-rich elements (AREs) in the 3' untranslated regions (UTR) of targeted mRNAs through their TZFs Lai & Blackshear, 2001;Lai et al, 1999;Lai et al, 2000), which leads to the removal of the poly(A) tail off the targeted mRNAs and promotes their degradation (Carrick et al, 2004;Lai & Blackshear, 2001). The ZFP36 family proteins are evolutionarily conserved, including four rodent members (ZFP36, ZFP36L1, ZFP36L2, and ZFP36L3) and three mammal members (with ZFP36L3 missing, Blackshear et al, 2005), each of which has two conserved ZF domains. Four members have been reported in Xenopus and zebrafish, among which ZFP36, ZFP36L1, and ZFP36L2 are conserved while the fourth member (Xenopus ZFP36L2.1, ZFP36L2.2 and zebrafish ZFCTH1) contains four ZF domains instead of two. The four ZFP36 genes in Xenopus have been cloned and are widely expressed in adult tissues, except for XZFP36L2.1 (XC3H-4), which is detected only in the ovary (De et al, 1999). It has been suggested that XZFP36L2b (XC3H-3b) plays an important role in Xenopus kidney development (Kaneko et al, 2003), but little is known about the roles of other ZFP36 members in embryonic development.
1Also known as cMG1, TIS11b, ERF1, BRF1, C3H-2, and Berg36 (Barnard et al, 1993;De et al, 1999;Lai et al, 1990;Varnum et al, 1991), ZFP36L1 has been reported to regulate vascular endothelial growth factor (VEGF) mRNA stability in adrenocorticotropic hormone-stimulated primary adrenocortical cells acting as a negative...