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BOR - Papers in Press, published online ahead of print April 6, 2005.
Biol Reprod 2005, 10.1095/biolreprod.105.040527
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BIOLOGY OF REPRODUCTION 73, 297–307 (2005)
DOI: 10.1095/biolreprod.105.040527
© 2005 by the Society for the Study of Reproduction, Inc.

Zfp36l3, a Rodent X Chromosome Gene Encoding a Placenta-Specific Member of the Tristetraprolin Family of CCCH Tandem Zinc Finger Proteins

Perry J. Blackshear 1 2,3,4  , Ruth S. Phillips 2, Sanjukta Ghosh 2, Silvia V.B. Ramos 2, Eric K. Richfield 5,6 , and Wi S. Lai 2

Laboratory of Neurobiology2 Office of Clinical Research,3 National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 Departments of Medicine and Biochemistry,4 Duke University Medical Center, Durham, North Carolina 27710 Department of Pathology and Lab Medicine,5 Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901 Molecular Histology Center,6 Environmental and Occupational Health Sciences Institute, University of Medicine and Dentistry, Piscataway, New Jersey 08854

Members of the tristetraprolin (TTP) family of CCCH tandem zinc finger (TZF) proteins can bind directly to AU-rich elements (ARE) in mRNA, causing deadenylation and destabilization of the transcripts to which they bind. We describe here a novel fourth mammalian member of the TTP protein family, designated ZFP36L3, which could also bind directly to ARE-containing RNAs and could promote the deadenylation and degradation of ARE-containing target RNAs. Zfp36l3 transcript expression was detected only in placenta and extraembryonic tissues in the mouse. It was expressed throughout development in the placenta and was particularly highly expressed in the cells of the labyrinthine layer of the trophoblastic placenta. Unlike the other family members, the expression of a ZFP36L3-green fluorescent protein fusion protein was entirely cytoplasmic when expressed in 293 cells, even in the presence of the CRM1-dependent nuclear export inhibitor leptomycin B. Zfp36l3 was located on the mouse X chromosome; a similar predicted gene was present on the rat X chromosome, but there was no evidence for a similar gene in humans. ZFP36L3 may thus be a rodent-specific or even murine-specific member of the TTP protein family. Its presumed role in placental physiology may be unique to rodents or murine rodents, but this role may be subsumed by other family members in nonrodents.

AU-rich element, cytokines, deadenylation, gene regulation, mRNA turnover, placenta, rodent-specific genes, trophoblast

1 Correspondence: P.J. Blackshear, A2-05 NIEHS, 111 Alexander Dr., Research Triangle Park, NC 27709. FAX 919 541 4571; black009{at}niehs.nih.gov




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