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首页> 外文期刊>Molecular and Cellular Biology >hnRNP C Is Required for Postimplantation Mouse Development but Is Dispensable for Cell Viability
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hnRNP C Is Required for Postimplantation Mouse Development but Is Dispensable for Cell Viability

机译：hnRNP C是植入后小鼠发育所必需的，但对于细胞生存力是必不可少的

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The hnRNP C1 and C2 proteins are among the most abundant proteins in the nucleus, and as ubiquitous components of RNP complexes, they have been implicated in many aspects of mRNA biogenesis. In this report, we have characterized a null mutation induced in embryonic stem cells by insertion of the U3His gene trap retrovirus into the first intron of the hnRNP C1/C2 gene. cDNAs encoding murine hnRNP C1 and C2 were characterized, and the predicted protein sequences were found to be highly conserved among vertebrates. A human consensus sequence, generated from over 400 expressed sequence tags, suggests two revisions to the previously published human sequence. In addition, alternatively spliced transcripts, expressed only by the murine gene, encode four novel proteins: variants of C1 and C2 with either seven additional amino acids or one fewer amino acid in a region between the oligomerization and C-terminal acidic domains. The disrupted gene was transmitted into the germ line and is tightly linked to a recessive, embryonic lethal phenotype. Homozygous mutant embryos fail to develop beyond the egg cylinder stage and are resorbed by 10.5 days of gestation, a phenotype consistent with a fundamental role in cellular metabolism. However, hnRNP C1 and C2 are not required for cell viability. Embryonic stem cell lines established from homozygous mutant blastocysts did not express detectable levels of either protein yet were able to grow and differentiate in vitro, albeit more slowly than wild-type cells. These results indicate that the C1 and C2 hnRNPs are not required for any essential step in mRNA biogenesis; however, the proteins may influence the rate and/or fidelity of one or more steps.
机译：hnRNP C1和C2蛋白是细胞核中含量最丰富的蛋白之一，它们作为RNP复合体的普遍成分，与mRNA生物合成的许多方面都有牵连。在本报告中，我们已经描述了通过将U3His基因陷阱逆转录病毒插入hnRNP C1 / C2基因的第一个内含子，在胚胎干细胞中诱导的无效突变。表征了编码鼠hnRNP C1和C2的cDNA，并且发现预测的蛋白序列在脊椎动物中高度保守。由超过400个表达的序列标签生成的人类共有序列建议对先前发布的人类序列进行两次修订。另外，仅由鼠基因表达的选择性剪接的转录本编码四种新蛋白：C1和C2的变体，在寡聚化和C末端酸性结构域之间的区域中具有七个额外的氨基酸或一个更少的氨基酸。破坏的基因被传递到种系中，并与隐性胚胎致死表型紧密相连。纯合突变体胚胎无法发育到卵筒期以外，并且在妊娠10.5天后被吸收，这种表型与细胞代谢中的基本作用一致。但是，hnRNP C1和C2对于细胞生存力不是必需的。从纯合突变胚泡中建立的胚胎干细胞系虽然不比野生型细胞慢，但却不能表达两种蛋白质的可检测水平，但能够在体外生长和分化。这些结果表明，C1和C2 hnRNPs对于mRNA生物发生中的任何必要步骤都不是必需的。但是，蛋白质可能会影响一个或多个步骤的速率和/或保真度。

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