Coccia E M, Cicala C, Charlesworth A, Ciccarelli C, Rossi G B, Philipson L, Sorrentino V
European Molecular Biology Laboratory, Heidelberg, Germany.
Mol Cell Biol. 1992 Aug;12(8):3514-21. doi: 10.1128/mcb.12.8.3514-3521.1992.
The growth arrest-specific gas5 gene was isolated from mouse genomic DNA and structurally characterized. The transcriptional unit is divided into 12 exons that span around 7 kb. An alternative splicing mechanism gives rise to two mature mRNAs which contain either 11 or 12 exons, and both are found in the cytoplasm of growth-arrested cells. In vivo, the gas5 gene is ubiquitously expressed in mouse tissues during development and adult life. In Friend leukemia and NIH 3T3 cells, the levels of gas5 gene mRNA were high in saturation density-arrested cells and almost undetectable in actively growing cells. Run-on experiments indicated that the gas5 gene is transcribed at the same level in both growing and arrested cells. On the other hand, in dimethyl sulfoxide-induced differentiating cells a sharp decrease in the rate of transcription was observed shortly before the cells reached the postmitotic stage. These results indicate that in density-arrested cells accumulation of gas5 mRNA is controlled at the posttranscriptional level while in differentiating cells expression is regulated transcriptionally.
生长停滞特异性gas5基因从小鼠基因组DNA中分离出来并进行了结构表征。转录单元被分为12个外显子，跨度约7kb。一种可变剪接机制产生了两种成熟的mRNA，它们分别包含11个或12个外显子，且在生长停滞细胞的细胞质中均有发现。在体内，gas5基因在小鼠发育和成年期的组织中普遍表达。在Friend白血病细胞和NIH 3T3细胞中，gas5基因mRNA水平在饱和密度停滞的细胞中较高，而在活跃生长的细胞中几乎检测不到。连续转录实验表明，gas5基因在生长和停滞的细胞中以相同水平转录。另一方面，在二甲基亚砜诱导分化的细胞中，在细胞到达有丝分裂后阶段前不久，观察到转录速率急剧下降。这些结果表明，在密度停滞的细胞中，gas5 mRNA的积累在转录后水平受到控制，而在分化细胞中，表达则受到转录调控。
