Cridge Andrew G, Major Louise L, Mahagaonkar Alhad A, Poole Elizabeth S, Isaksson Leif A, Tate Warren P
Department of Biochemistry, University of Otago, PO Box 56, Dunedin, New Zealand.
Nucleic Acids Res. 2006 Apr 13;34(7):1959-73. doi: 10.1093/nar/gkl074. Print 2006.
Six diverse prokaryotic and five eukaryotic genomes were compared to deduce whether the protein synthesis termination signal has common determinants within and across both kingdoms. Four of the six prokaryotic and all of the eukaryotic genomes investigated demonstrated a similar pattern of nucleotide bias both 5' and 3' of the stop codon. A preferred core signal of 4 nt was evident, encompassing the stop codon and the following nucleotide. Codons decoded by hyper-modified tRNAs were over-represented in the region 5' to the stop codon in genes from both kingdoms. The origin of the 3' bias was more variable particularly among the prokaryotic organisms. In both kingdoms, genes with the highest expression index exhibited a strong bias but genes with the lowest expression showed none. Absence of bias in parasitic prokaryotes may reflect an absence of pressure to evolve more efficient translation. Experiments were undertaken to determine if a correlation existed between bias in signal abundance and termination efficiency. In Escherichia coli signal abundance correlated with termination efficiency for UAA and UGA stop codons, but not in mammalian cells. Termination signals that were highly inefficient could be made more efficient by increasing the concentration of the cognate decoding release factor.
比较了六个不同的原核生物基因组和五个真核生物基因组，以推断蛋白质合成终止信号在两个界内和界间是否具有共同的决定因素。所研究的六个原核生物基因组中的四个以及所有真核生物基因组在终止密码子的5'和3'端均表现出相似的核苷酸偏向模式。一个明显的4个核苷酸的首选核心信号，包括终止密码子和其后的核苷酸。由超修饰tRNA解码的密码子在两个界的基因中终止密码子5'端区域中过度富集。3'端偏向的起源更具变异性，特别是在原核生物中。在两个界中，具有最高表达指数的基因表现出强烈的偏向，但表达最低的基因则没有偏向。寄生原核生物中缺乏偏向可能反映出缺乏进化出更高效翻译的压力。进行实验以确定信号丰度的偏向与终止效率之间是否存在相关性。在大肠杆菌中，信号丰度与UAA和UGA终止密码子的终止效率相关，但在哺乳动物细胞中则不然。通过增加同源解码释放因子的浓度，可以使效率极低的终止信号变得更有效。
