Comparative Functional Analysis of ZFP36 Genes during Xenopus Development

Abstract

ZFP36 constitutes a small family of RNA binding proteins (formerly known as the TIS11 family) that target mRNA and promote their degradation. In mammals, ZFP36 proteins are encoded by four genes and, although they show similar activities in a cellular RNA destabilization assay, there is still a limited knowledge of their mRNA targets and it is not known whether or not they have redundant functions. In the present work, we have used the Xenopus embryo, a model system allowing gain- and loss-of-function studies, to investigate, whether individual ZFP36 proteins had distinct or redundant functions. We show that overexpression of individual amphibian zfp36 proteins leads to embryos having the same defects, with alteration in somites segmentation and pronephros formation. In these embryos, members of the Notch signalling pathway such as hairy2a or esr5 mRNA are down-regulated, suggesting common targets for the different proteins. We also show that mouse Zfp36 protein overexpression gives the same phenotype, indicating an evolutionary conserved property among ZFP36 vertebrate proteins. Morpholino oligonucleotide-induced loss-of-function leads to defects in pronephros formation, reduction in tubule size and duct coiling alterations for both zfp36 and zfp36l1, indicating no functional redundancy between these two genes. Given the conservation in gene structure and function between the amphibian and mammalian proteins and the conserved mechanisms for pronephros development, our study highlights a potential and hitherto unreported role of ZFP36 gene in kidney morphogenesis.

zfp36 expression delineates both myeloid cells and cells localized to the fusing neural folds in Xenopus tropicalis

“…1). Consistent with the study of Tréguer and colleagues (Tréguer et al, 2013) a punctate staining was present at both stages. In late neurula (st. 20), this labelling was centered on the ventral region that corresponds likely to the aVBI while at stage 26 the labelled cells extended all over the surface of the embryo.…”

“…Considering that ZFP36 is a protein with a prevalent role in the control of inflammatory process, we hypothesized that the punctate staining observed by Treguer and colleagues (Tréguer et al, 2013) could be originating from the population of migratory macrophages. To address this hypothesis we first tested wether the published staining pattern was reproducible in X. tropicalis.…”

“…In Xenopus laevis, a fourth member previously called C3H4 and named Zfp36L4 has been identified (Belloc and Méndez, 2008;De et al, 1999;Tréguer et al, 2013).…”

“…It is also rapidly induced in macrophages following their activation by bacterial pathogens (Nau et al, 2002). A recent study on the ZFP36 family of RNA binding protein in Xenopus laevis presented the expression pattern for the 4 members of this family (Tréguer et al, 2013). Particularly, the expression pattern of zfp36 was presented from stage 24 to stage 34.…”

Tristetraprolin expression and microRNA-mediated regulation during simian immunodeficiency virus infection of the central nervous system

“…Tristetraprolin (TTP, also known as zinc finger protein 36 homolog, ZFP36) has been characterized as an anti-inflammatory and anticarcinogenic protein that is also involved in differentiation processes [16,17]. TTP is thought to act primarily through post-transcriptional regulation of messenger RNA [18,19].…”