title: Characterization of DeltaN-Zfp36l2 mutant associated with arrest of early embryonic development and female infertility.
abstract: The zinc finger protein 36-like 2, Zfp36l2, has been implicated in female mouse infertility, because an amino-terminal truncation mutation (ΔN-Zfp36l2) leads to two-cell stage arrest of embryos derived from the homozygous mutant female gamete. Zfp36l2 is a member of the tristetraprolin (TTP) family of CCCH tandem zinc finger proteins that can bind to transcripts containing AU-rich elements (ARE), resulting in deadenylation and destabilization of these transcripts. I show here that the mouse Zfp36l2 is composed of two exons and a single intron, encoding a polypeptide of 484 amino acids. I observed that ΔN-Zfp36l2 protein is similar to both wild-type Zfp36l2 and TTP (Zfp36) in that it shuttles between the cytoplasm and nucleus, binds to RNAs containing AREs, and promotes deadenylation of a model ARE transcript in a cell-based co-transfection assay. Surprisingly, in contrast to TTP, Zfp36l2 mRNA and protein were rapidly down-regulated upon LPS exposure in bone marrow-derived macrophages. The ΔN-Zfp36l2 protein was substantially more resistant to stimulus-induced down-regulation than the WT. I postulate that the embryonic arrest linked to the ΔN-Zfp36l2 truncation might be related to its resistance to stimulus-induced down-regulation.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of North Carolina, School of Medicine, Chapel Hill, North Carolina 27599, USA.
authors.forename: Silvia B V
authors.initials: SB
authors.lastname: Ramos
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D029681:Arabidopsis Proteins / Q000502:physiology; D051817:Butyrate Response Factor 1; D015536:Down-Regulation / Q000502:physiology; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006801:Humans; D007247:Infertility, Female / Q000235:genetics* / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000502:physiology
chemical_list: D029681:Arabidopsis Proteins; D051817:Butyrate Response Factor 1; D009687:Nuclear Proteins; C532627:POK protein, Arabidopsis; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D033921:Vesicular Transport Proteins; C488431:Zfp36l1 protein, mouse; D000249:Adenosine Monophosphate