Aberrant mRNAs with extended 3′ UTRs are substrates for rapid degradation by mRNA surveillance
Aberrant mRNAs with extended 3′ UTRs are substrates for rapid degradation by mRNA surveillance
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DOI：
10.1017/s1355838299990829
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发表时间：
1999-10-01
期刊：
影响因子：
4.5
通讯作者：
Parker, R
中科院分区：
文献类型：
--
作者：
Muhlrad, D;Parker, R
已知mRNA监视系统在称为无义介导的衰变的过程中快速降解含有提前终止密码子的异常mRNA。第二类异常mRNA是其中3' UTR由于多聚腺苷酸化位点中的突变而异常延伸的那些。我们提供了几个观察结果，这些异常的3 '-延伸的mRNA被降解具有过早无义密码子的mRNA的相同机制降解。首先，3 '-延伸的mRNA的衰变依赖于相同的脱帽酶和5'-至-3 '核酸外切酶。其次，衰变也依赖于UPF 1、UPF 2和UPF 3基因编码的蛋白质，已知这些蛋白质是含有无义密码子的mRNA快速衰变所特异性需要的。第三，通过稳定PGK 1编码区内的序列来防止延伸的3' UTR触发衰变的能力，已知PGK 1编码区内的序列保护mRNA免受过早无义密码子诱导的快速衰变。这些结果表明mRNA监视系统在降解异常延伸的3' UTR中起作用。我们提出了一种模型，其中mRNA监视机制降解异常mRNA，这是由于缺乏相对于3 ′ UTR元件的终止-终止密码子的适当空间排列，如利用多聚腺苷酸化位点所定义的。
The mRNA surveillance system is known to rapidly degrade aberrant mRNAs that contain premature termination codons in a process referred to as nonsense-mediated decay, A second class of aberrant mRNAs are those wherein the 3' UTR is abnormally extended due to a mutation in the polyadenylation site. We provide several observations that these abnormally 3'-extended mRNAs are degraded by the same machinery that degrades mRNAs with premature nonsense codons. First, the decay of the 3'-extended mRNAs is dependent on the same decapping enzyme and 5'-to-3' exonuclease. Second, the decay is also dependent on the proteins encoded by the UPF1, UPF2, and UPF3 genes, which are known to be specifically required for the rapid decay of mRNAs containing nonsense codons. Third, the ability of an extended 3' UTR to trigger decay is prevented by stabilizing sequences within the PGK1 coding region that are known to protect mRNAs from the rapid decay induced by premature nonsense codons, These results indicate that the mRNA surveillance system plays a role in degrading abnormally extended 3' UTRs, Based on these results, we propose a model in which the mRNA surveillance machinery degrades aberrant mRNAs due to the absence of the proper spatial arrangement of the translation-termination codon with respect to the 3' UTR element as defined by the utilization of a polyadenylation site.