MESSENGER-RNA SURVEILLANCE BY THE CAENORHABDITIS-ELEGANS SMG GENES
MESSENGER-RNA SURVEILLANCE BY THE CAENORHABDITIS-ELEGANS SMG GENES
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DOI：
10.1101/gad.7.10.1885
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发表时间：
1993-10-01
影响因子：
10.5
通讯作者：
ANDERSON, P
中科院分区：
文献类型：
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作者：
PULAK, R;ANDERSON, P
含有提前终止密码子的mRNA在大多数真核生物中是不稳定的，但其降解机制在很大程度上是未知的。我们证明了六个C的功能。秀丽线虫smg基因对于unc-54肌球蛋白重链基因的无义突变体mRNA的快速转换是必需的。unc-54的无义等位基因表达的mRNA在smg（+）遗传背景下不稳定，但在smg（-）背景下具有正常或接近正常的稳定性。sMG突变还稳定UNC-54（R293）的mRNA，这是一种去除UNC-54多聚腺苷酸化位点并表达异常mRNA的小缺失。大多数unc-54无义突变在smg（+）和smg（-）遗传背景下都是隐性的。而4个特异等位基因在smg（+）时为隐性，在smg（-）时为显性。这些smg依赖的显性等位基因表达无义突变多肽，破坏粗丝和/或肌节组装。预测所有四个等位基因表达无义片段多肽，其含有大部分肌球蛋白球状头部结构域而没有附着的杆段。通过降解含有过早终止密码子的信息，smg基因消除了编码潜在毒性蛋白质片段的mRNA。我们认为，这种mRNA周转系统保护细胞免受自身转录、mRNA加工或mRNA转运错误的影响。
mRNAs that contain premature stop codons are unstable in most eukaryotes, but the mechanism of their degradation is largely unknown. We demonstrate that functions of the six C. elegans smg genes are necessary for rapid turnover of nonsense mutant mRNAs of the unc-54 myosin heavy chain gene. Nonsense alleles of unc-54 express mRNAs that are unstable in smg(+) genetic backgrounds but have normal or near normal stability in smg(-) backgrounds. smg mutations also stabilize mRNA of unc-54(r293), a small deletion that removes the unc-54 polyadenylation site and expresses an aberrant mRNA. Most unc-54 nonsense mutations are recessive in both smg(+) and smg(-) genetic backgrounds. However, four specific alleles are recessive when smg(+) and dominant when smg(-). These smg-dependent dominant alleles express nonsense mutant polypeptides that disrupt thick filament and/or sarcomere assembly. All four alleles are predicted to express nonsense fragment polypeptides that contain most of the myosin globular head domain without an attached rod segment. By degrading messages that contain premature stop codons, the smg genes eliminate mRNAs that encode potentially toxic protein fragments. We propose that this system of mRNA turnover protects cells from their own errors of transcription, mRNA processing, or mRNA transport.