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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Molecular coevolution of mammalian ribosomal gene terminator sequences and the transcription termination factor TTF-I.
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Molecular coevolution of mammalian ribosomal gene terminator sequences and the transcription termination factor TTF-I.

机译:哺乳动物核糖体基因终止子序列与转录终止因子TTF-1的分子协同进化。

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摘要

Both the DNA elements and the nuclear factors that direct termination of ribosomal gene transcription exhibit species-specific differences. Even between mammals--e.g., human and mouse--the termination signals are not identical and the respective transcription termination factors (TTFs) which bind to the terminator sequence are not fully interchangeable. To elucidate the molecular basis for this species-specificity, we have cloned TTF-I from human and mouse cells and compared their structural and functional properties. Recombinant TTF-I exhibits species-specific DNA binding and terminates transcription both in cell-free transcription assays and in transfection experiments. Chimeric constructs of mouse TTF-I and human TTF-I reveal that the major determinant for species-specific DNA binding resides within the C terminus of TTF-I. Replacing 31 C-terminal amino acids of mouse TTF-I with the homologous human sequences relaxes the DNA-binding specificity and, as a consequence, allows the chimeric factor to bind the human terminator sequence and to specifically stop rDNA transcription.
机译:指导核糖体基因转录终止的DNA元素和核因子均表现出物种特异性差异。即使在哺乳动物之间(例如人和小鼠),终止信号也不相同,并且与终止子序列结合的相应转录终止因子(TTF)也不能完全互换。为了阐明这种物种特异性的分子基础,我们从人和小鼠细胞中克隆了TTF-1,并比较了它们的结构和功能特性。重组TTF-1在无细胞转录测定和转染实验中均表现出物种特异性的DNA结合并终止转录。小鼠TTF-1和人TTF-1的嵌合构建体揭示了物种特异性DNA结合的主要决定因素位于TTF-1的C末端内。用同源的人序列取代小鼠TTF-1的31个C端氨基酸可放松DNA结合特异性,结果,可使嵌合因子结合人终止子序列并特异性地终止rDNA转录。

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