Premature termination of <i>GAT1</i> transcription explains paradoxical negative correlation between nitrogen-responsive mRNA, but constitutive low-level protein production
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The first step in executing the genetic program of a cell is production of mRNA. In yeast, almost every gene is transcribed as multiple distinct isoforms, differing at their 5′ and/or 3′ termini. However, the implications and functional significance of the transcriptome-wide diversity of mRNA termini remains largely unexplored. In this paper, we show that the <i>GAT1</i> gene, encoding a transcriptional activator of nitrogen-responsive catabolic genes, produces a variety of mRNAs differing in their 5′ and 3′ termini. Alternative transcription initiation leads to the constitutive, low level production of 2 full length proteins differing in their N-termini, whereas premature transcriptional termination generates a short, highly nitrogen catabolite repression- (NCR-) sensitive transcript that, as far as we can determine, is not translated under the growth conditions we used, but rather likely protects the cell from excess Gat1.
细胞遗传程序执行的首要步骤为信使RNA(mRNA)的生成。在酵母中,几乎所有基因均可转录产生多种不同的异构体,这些异构体的差异体现在5′和/或3′末端区域。然而,全转录组范围内mRNA末端多样性的潜在影响与功能意义,目前仍未得到充分探索。本研究证实,编码氮响应分解代谢基因转录激活因子的GAT1基因,可生成一系列5′与3′末端存在差异的mRNA亚型。可变转录起始会持续低水平表达两种N末端存在差异的全长蛋白;而提前转录终止则会产生一段较短的、对氮分解代谢阻遏(NCR)高度敏感的转录本。据我们目前所能确定的是,该转录本在所使用的培养条件下并未发生翻译,反而大概率可帮助细胞抵御过量Gat1蛋白带来的负面影响。




