Murgola E J, Hijazi K A, Göringer H U, Dahlberg A E
Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Proc Natl Acad Sci U S A. 1988 Jun;85(12):4162-5. doi: 10.1073/pnas.85.12.4162.
We have isolated an unusual codon-specific translational suppressor in Escherichia coli. The suppressor resulted from a spontaneous mutation in a chromosomal gene during a selection for suppressors of the auxotrophic nonsense mutation trpA(UGA211). The suppressor allows readthrough of UGA mutations at two positions in trpA and at two sites in bacteriophage T4. It does not, however, suppress amber (UAG) or ochre (UAA) mutations that were tested in both genomes, some of which were at the same positions as the suppressible UGA mutations. The suppressor also does not allow mistranslation of the UGA-related trpA missense mutations UGG at positions 211 and 234, AGA at 211 and 234, CGA at 211, or UGU and UGC at 234. The suppressor mutation was mapped by genetic procedures to position 89 on the E. coli genetic map. Localization of the suppressor mutation to rrnB was achieved by cloning it in the low-copy-number plasmid pEJM007 by in vivo recombination from the chromosome. Recloning in bacteriophage M13 and subsequent DNA sequence analysis allowed the identification of the suppressor mutation as a deletion of the cytidylic acid residue at nucleotide position 1054 of the 16S ribosomal RNA. The mutant EcoRI-Xba I fragment from the suppressor gene was recloned, from M13, in an otherwise wild-type rrnB in the plasmid pEJM007, and UGA suppression was examined. The UGA-suppressing activity of the reconstructed suppressor-containing pEJM007 was indistinguishable from that of the original recombinant suppressor-containing plasmid. This result demonstrates that the C1054 deletion in 16S rRNA is both necessary and sufficient for UGA suppression. The existence of this mutant suggests an important role for rRNA in codon recognition, at least for accurate polypeptide chain termination.
我们在大肠杆菌中分离出了一种不寻常的密码子特异性翻译抑制子。该抑制子是在对营养缺陷型无义突变trpA(UGA211)的抑制子进行筛选过程中,由染色体基因的自发突变产生的。该抑制子能使trpA基因中两个位置以及噬菌体T4中两个位点的UGA突变实现通读。然而,它不能抑制在两个基因组中测试的琥珀色(UAG)或赭石色(UAA)突变,其中一些与可抑制的UGA突变位于相同位置。该抑制子也不能使UGA相关的trpA错义突变UGG(位于211和234位)、AGA(位于211和234位)、CGA(位于211位)或UGU和UGC(位于234位)发生错义翻译。通过遗传方法将抑制子突变定位到大肠杆菌遗传图谱上的89位。通过体内重组从染色体上将抑制子突变克隆到低拷贝数质粒pEJM007中,从而将其定位到rrnB。在噬菌体M13中重新克隆并随后进行DNA序列分析,确定抑制子突变是16S核糖体RNA核苷酸位置1054处的胞苷酸残基缺失。来自抑制子基因的突变EcoRI - Xba I片段从M13重新克隆到质粒pEJM007中原本野生型的rrnB中,并检测UGA抑制情况。重建的含抑制子的pEJM007的UGA抑制活性与原始含重组抑制子的质粒的活性没有区别。这一结果表明16S rRNA中的C1054缺失对于UGA抑制既是必要的也是充分的。这种突变体的存在表明rRNA在密码子识别中具有重要作用,至少对于准确的多肽链终止是如此。