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首页> 外文期刊>Molecular and Cellular Biology >Introns are cis effectors of the nonsense-codon-mediated reduction in nuclear mRNA abundance.
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Introns are cis effectors of the nonsense-codon-mediated reduction in nuclear mRNA abundance.

机译：内含子是无义密码子介导的核mRNA丰度降低的顺式效应子。

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The translation of human triosephosphate isomerase (TPI) mRNA normally terminates at codon 249 within exon 7, the final exon. Frameshift and nonsense mutations of the type that cause translation to terminate prematurely at or upstream of codon 189 within exon 6 reduce the level of nuclear TPI mRNA to 20 to 30% of normal by a mechanism that is not a function of the distance of the nonsense codon from either the translation initiation or termination codon. In contrast, frameshift and nonsense mutations of another type that cause translation to terminate prematurely at or downstream of codon 208, also within exon 6, have no effect on the level of nuclear TPI mRNA. In this work, quantitations of RNA that derived from TPI alleles in which nonsense codons had been generated between codons 189 and 208 revealed that the boundary between the two types of nonsense codons resides between codons 192 and 195. The analysis of TPI gene insertions and deletions indicated that the positional feature differentiating the two types of nonsense codons is the distance of the nonsense codon upstream of intron 6. For example, the movement of intron 6 to a position downstream of its normal location resulted in a concomitant downstream movement of the boundary between the two types of nonsense codons. The analysis of intron 6 mutations indicated that the intron 6 effect is stipulated by the 88 nucleotides residing between the 5' and 3' splice sites. Since the deletion of intron 6 resulted in only partial abrogation of the nonsense codon-mediated reduction in the level of TPI mRNA, other sequences within TPI pre-mRNA must function in the effect. One of these sequences may be intron 2, since the deletion of intron 2 also resulted in partial abrogation of the effect. In experiments that switched introns 2 and 6, the replacement of intron 6 with intron 2 was of no consequence to the effect of a nonsense codon within either exon 1 or exon 6. In contrast, the replacement of intron 2 with intron 6 was inconsequential to the effect of a nonsense codon in exon 6 but resulted in partial abrogation of a nonsense codon in exon 1.
机译：人磷酸丙糖异构酶（TPI）mRNA的翻译通常终止于第7外显子（最终外显子）的249位密码子。导致翻译在外显子6内第189位密码子处或上游过早终止的类型的移码和无义突变，通过不依赖于无义距离的机制将核TPI mRNA水平降低至正常值的20％至30％来自翻译起始密码子或终止密码子的密码子。相反，导致翻译在密码子208处或下游（也位于外显子6内）过早终止的另一种移码和无义突变对核TPI mRNA水平没有影响。在这项工作中，对源自在189和208号密码子之间产生无义密码子的TPI等位基因衍生的RNA的定量分析表明，两种类型的无义密码子之间的边界位于192和195号密码子之间。TPI基因插入和缺失分析指出区分两种类型的无义密码子的位置特征是内含子6上游的无义密码子的距离。例如，内含子6向其正常位置下游位置的移动导致了内含子6之间的边界随之向下游移动。两种类型的无用密码子。对内含子6突变的分析表明，内含子6的作用由5'和3'剪接位点之间的88个核苷酸规定。由于内含子6的缺失仅导致无义密码子介导的TPI mRNA水平降低的部分废除，因此TPI前mRNA中的其他序列必须发挥作用。这些序列之一可能是内含子2，因为内含子2的缺失也导致该效应的部分废除。在转换内含子2和6的实验中，用内含子2取代内含子6并不影响外显子1或外显子6内无义密码子的作用。相反，用内含子6取代内含子2对第6外显子无意义密码子的作用，但导致第1外显子无意义密码子的部分废除。

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