Chen Shun-Jia, Ko Chou-Yuan, Yen Chih-Wei, Wang Chien-Chia
Department of Life Science, National Central University, Jung-li 320, Taiwan.
J Biol Chem. 2009 Jan 9;284(2):818-27. doi: 10.1074/jbc.M804378200. Epub 2008 Nov 14.
Earlier studies showed that the redundancy of ACG initiation codons enhanced the efficiency of translation initiation by 3- to 6-fold. Evidence presented here shows that this "redundancy effect" can be attributed to a favorable sequence context and, to a lesser extent, remedial initiation. In the case of redundant ACG initiator codons, the second ACG not only acts as a remedial initiation site for scanning ribosomes that skip the first ACG but also enhances the activity of the preceding initiator by providing a preferable "A" at its relative +4 position. Hence, non-successive ACG codons can be as effective as successive ACG codons in initiation, if positioned within a similar context. In contrast, redundant GUG initiation codons (GUG/GUG) bear an unfavorable "G" nucleotide at both the +4 and -3 positions relative to the first and second GUGs, respectively, such that redundant GUG codons act more poorly as translation initiation sites than does a single GUG with a favorable "A" nucleotide in the +4 position ( approximately 2.5-fold). Thus, the sequence context plays a much more important role than remedial initiation in modulating the efficiency of translational initiation from redundant non-AUG codons.
早期研究表明，ACG起始密码子的冗余使翻译起始效率提高了3至6倍。此处提供的证据表明，这种“冗余效应”可归因于有利的序列上下文，在较小程度上也可归因于补救起始。对于冗余的ACG起始密码子，第二个ACG不仅作为扫描核糖体跳过第一个ACG后的补救起始位点，还通过在其相对+4位置提供一个更优的“A”来增强前一个起始密码子的活性。因此，如果位于相似的上下文中，非连续的ACG密码子在起始方面可以与连续的ACG密码子一样有效。相比之下，冗余的GUG起始密码子（GUG/GUG）在相对于第一个和第二个GUG的+4和-3位置分别带有一个不利的“G”核苷酸，因此冗余的GUG密码子作为翻译起始位点的作用比在+4位置带有一个有利的“A”核苷酸的单个GUG要差得多（约2.5倍）。因此，在调节来自冗余非AUG密码子的翻译起始效率方面，序列上下文比补救起始起着更为重要的作用。
