RBM19 is essential for preimplantation development in the mouse.
BACKGROUND
RNA-binding motif protein 19 (RBM19, NCBI Accession # NP_083038) is a conserved nucleolar protein containing 6 conserved RNA recognition motifs. Its biochemical function is to process rRNA for ribosome biogenesis, and it has been shown to play a role in digestive organ development in zebrafish. Here we analyzed the role of RBM19 during mouse embryonic development by generating mice containing a mutation in the Rbm19 locus via gene-trap insertion.


RESULTS
Homozygous mutant embryos failed to develop beyond the morula stage, showing defective nucleologenesis, activation of apoptosis, and upregulation of P53 target genes. A unique feature of RBM19 is its localization to the cytoplasm in morula stage-embryos, whereas most other nucleolar proteins are localized to the nucleolar precursor body (NPB). The nucleoli in the Rbm19 mutant embryos remain immature, yet they can carry out rRNA synthesis. The timing of developmental arrest occurs after expression of the inner cell mass markers OCT3/4 and NANOG, but prior to the specification of trophectoderm as reflected by CDX2 expression.


CONCLUSIONS
The data indicate that RBM19 is essential for preimplantation development, highlighting the importance of de novo nucleologenesis during this critical developmental stage.
Zhang
Jian
J
Division of Gastroenterology, Department of Pediatrics, Medical College of Wisconsin and Children's Research Institute, Milwaukee, WI 53226, USA. jzhang@mcw.edu
Tomasini
Amber J
AJ
Mayer
Alan N
AN
D000818:Animals; D017209:Apoptosis; D001324:Autoantigens / Q000378:metabolism; D001483:Base Sequence; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D001757:Blastomeres / Q000166:cytology / Q000648:ultrastructure; D015820:Cadherins / Q000378:metabolism; D002466:Cell Nucleolus / Q000648:ultrastructure; D047108:Embryonic Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009028:Morula / Q000166:cytology / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011247:Pregnancy; D021381:Protein Transport; D012335:RNA, Ribosomal / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D001324:Autoantigens; D015820:Cadherins; D009687:Nuclear Proteins; D012335:RNA, Ribosomal; D016601:RNA-Binding Proteins; C539474:Rbm19 protein, mouse; D016159:Tumor Suppressor Protein p53