Distribution of rare triplets along mRNA and their relation to protein folding
Distribution of rare triplets along mRNA and their relation to protein folding
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DOI：
10.1080/07391102.2002.10506859
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发表时间：
2002-12-01
影响因子：
4.4
通讯作者：
Trifonov, EN
中科院分区：
文献类型：
--
作者：
Makhoul, CH;Trifonov, EN
据信，mRNA翻译过程中的停顿在确保蛋白质链的新合成部分的正确折叠方面起着一定的作用。当mRNA中遇到罕见的三联体时，会发生这种暂停，因为它需要额外的时间来递送相应的罕见tRNA。为了确定是否暂停网站是非随机分布的沿着原核mRNA（cDNA），我们已经找到了集群的罕见三联体的cDNA序列从21种不同的细菌。从用各种窗口计算的局部密码子频率的个人概况，最稀有密码子的簇的位置被用于产生暂停位点的位置偏好的组合直方图。直方图显示，在原核生物序列中，暂停位点优先位于起始位置和从起始位置起约155个三联体处。为了验证这些观察结果的普遍性，将数据分为六个独立的组，每组约500个序列，所有序列都显示相同的特征。在三重态位置75处也看到不太突出的最大值。根据155个三重峰处的峰值幅度判断，估计最佳簇大小等于18个三重峰。距离155紧密对应于典型蛋白质折叠的大小和早期估计的原核蛋白质序列片段。这支持了翻译暂停在蛋白质结构域的共翻译折叠中的作用的建议。mRNA中稀有密码子的谱可以用于检测或预测蛋白质结构域之间的边界。
It is believed that pausing during mRNA translation plays some role in ensuring proper folding of newly synthesized sections of a protein chain. Such pausing occurs when rare triplets are encountered in the mRNA, as it takes additional time for the corresponding rare species of tRNA to be delivered. To determine whether pause sites are non-randomly distributed along prokaryotic mRNA (cDNA), we have located clusters of rare triplets in cDNA sequences from 21 different bacteria. From the individual profiles of local codon frequencies calculated with various windows, the positions of the clusters of the rarest codons were taken for generation of the combined histograms of positional preferences of the pause sites. The histograms show that in the prokaryotic sequences, the pause sites are located preferentially at the start positions and at about 155 triplets from the starts. To verify the generality of these observations, the data are grouped in six independent sets about 500 sequences each, all revealing the same features. A less prominent maximum is also seen at the triplet position 75. Judging by the amplitude of the peak at 155 triplets, an optimal cluster size is estimated to equal 18 triplets. The distance 155 closely corresponds to the sizes of typical protein folds and to earlier estimated prokaryotic protein sequence segments. This supports the suggestion of a role for translation pausing in the cotranslational folding of protein domains. The profiles of rare codons in mRNA can serve in the detection or prediction of boundaries between protein domains.