DOWNSTREAM SECONDARY STRUCTURE FACILITATES RECOGNITION OF INITIATOR CODONS BY EUKARYOTIC RIBOSOMES
DOWNSTREAM SECONDARY STRUCTURE FACILITATES RECOGNITION OF INITIATOR CODONS BY EUKARYOTIC RIBOSOMES
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DOI：
10.1073/pnas.87.21.8301
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发表时间：
1990-11-01
影响因子：
11.1
通讯作者：
KOZAK, M
中科院分区：
文献类型：
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作者：
KOZAK, M
当在蛋白质编码序列的开始附近引入适量的二级结构时，在次优背景下AUG起始密码子的识别得到改善。这种促进作用取决于下游茎环（发夹）结构的位置。当发夹与前面的AUG密码子相隔14个核苷酸时，观察到最强的促进作用。因为14个核苷酸对应于核糖体的前缘与其AUG识别中心之间的近似距离，如通过核糖核酸酶保护实验所测量的，对下游发夹的增强作用的可能解释是二级结构减慢扫描，从而为AUG密码子的识别提供更多时间，当40 S核糖体的AUG识别中心直接位于AUG上时，这种促进作用最大。哺乳动物核糖体在体外启动非AUG密码子的可变能力也可以通过是否存在茎-环结构正好位于替代起始密码子的下游。这可能与最近报道的一些脊椎动物mRNA中具有结构倾向性、富含G+ C的前导序列的非AUG密码子处的偶然上游起始事件有关。
Recognition of an AUG initiator codon in a suboptimal context improves when a modest amount of secondary structure is introduced near the beginning of the protein-coding sequence. This facilitating effect depends on the position of the downstream stem-loop (hairpin) structure. The strongest facilitation is seen when the hairpin is separated from the preceding AUG codon by 14 nucleotides. Because 14 nucleotides corresponds to the approximate distance between the leading edge of the ribosome and its AUG-recognition center as measured by ribonuclease protection experiments, a likely explanation for the enhancing effect of a downstream hairpin is that secondary structure slows scanning, thereby providing more time for recognition of the AUG codon, and the facilitation is greatest when the 40S ribosome stalls with its AUG-recognition center directly over the AUG. The variable ability of mammalian ribosomes to initiate at non-AUG codons in vitro is also explicable by the presence or absence of a stem-loop structure just downstream from the alternative initiator codon. This may be relevant to recent reports of adventitious upstream initiation events at non-AUG codons in some vertebrate mRNAs that have structure-prone, G+C-rich leader sequences.