Zhang Jian, Tomasini Amber J, Mayer Alan N
Division of Gastroenterology, Department of Pediatrics, Medical College of Wisconsin and Children's Research Institute, Milwaukee, WI 53226, USA.
BMC Dev Biol. 2008 Dec 16;8:115. doi: 10.1186/1471-213X-8-115.
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.
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.
The data indicate that RBM19 is essential for preimplantation development, highlighting the importance of de novo nucleologenesis during this critical developmental stage.
RNA结合基序蛋白19（RBM19，NCBI登录号#NP_083038）是一种保守的核仁蛋白，含有6个保守的RNA识别基序。其生化功能是加工用于核糖体生物合成的rRNA，并且已证明它在斑马鱼的消化器官发育中起作用。在这里，我们通过基因捕获插入产生Rbm19基因座发生突变的小鼠，分析了RBM19在小鼠胚胎发育过程中的作用。
纯合突变胚胎在桑椹胚阶段后无法发育，表现出核仁发生缺陷、细胞凋亡激活和P53靶基因上调。RBM19的一个独特特征是其在桑椹胚阶段胚胎中定位于细胞质，而大多数其他核仁蛋白定位于核仁前体（NPB）。Rbm19突变胚胎中的核仁仍然不成熟，但它们可以进行rRNA合成。发育停滞的时间发生在内细胞团标记物OCT3/4和NANOG表达之后，但在由CDX2表达反映的滋养外胚层特化之前。
数据表明RBM19对植入前发育至关重要，突出了在这个关键发育阶段从头进行核仁发生的重要性。
