The yeast cytoplasmic LsmI/Pat1p complex protects mRNA 3' termini from partial degradation.
The yeast cytoplasmic LsmI/Pat1p complex protects mRNA 3' termini from partial degradation.
复制标题
酵母细胞质 LsmI/Pat1p 复合物可保护 mRNA 3 末端免于部分降解。
DOI：
10.1093/genetics/158.4.1445
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发表时间：
2001
期刊：
影响因子：
3.3
通讯作者：
Parker,R
中科院分区：
文献类型：
--
作者：
He,W;Parker,R
了解真核基因调控的一个关键方面是识别和分析结合 mRNA 并控制其功能的蛋白质。最近，七个 Lsm 蛋白和 Pat1p 的复合物已被证明可以与酵母 mRNA 相互作用并促进 mRNA 脱帽。在这项研究中，我们提出了一些观察结果，表明 LsmI/Pat1 复合物在保护 mRNA 的 3'-UTR 免于修剪方面具有第二个独特的功能。首先，LSM1 至 LSM7 以及 PAT1 基因的突变导致 MFA2pG 和 PGK1pG 转录本的积累，这些转录本在 3' 端被缩短了 10-20 个核苷酸（称为修剪）。其次，这些 mRNA 的修剪在高温下更为严重，这与这些突变株无法在高温下生长有关。相反，在缺乏脱帽酶的 adcp1Δ 菌株中没有发生修剪。这表明修剪不仅仅是抑制 mRNA 脱帽的结果。第三，lsmandpat1突变体的温度敏感性生长受到外泌体或功能相关Ski蛋白突变的抑制，这些突变是mRNA从3'端到5'端mRNA有效降解所必需的。此外，在lsm skidouble突变体中，积累了更高水平的修剪的mRNA，这表明外泌体功能不是mRNA修剪所必需的，但外泌体确实降解了修剪的mRNA。这些结果提出了一种可能性，即 lsm1-7 和 pat1 突变体的温度敏感生长至少部分是由于 mRNA 修剪，这要么使 mRNA 的功能失活，要么使它们可被外泌体过早地进行 3' 至 5' 降解。
A key aspect of understanding eukaryotic gene regulation will be the identification and analysis of proteins that bind mRNAs and control their function. Recently, a complex of seven Lsm proteins and the Pat1p have been shown to interact with yeast mRNAs and promote mRNA decapping. In this study we present several observations to indicate that the LsmI/Pat1 complex has a second distinct function in protecting the 3′-UTR of mRNAs from trimming. First, mutations in theLSM1toLSM7, as well asPAT1, genes led to the accumulation ofMFA2pGandPGK1pGtranscripts that had been shortened by 10–20 nucleotides at their 3′ ends (referred to as trimming). Second, the trimming of these mRNAs was more severe at the high temperature, correlating with the inability of these mutant strains to grow at high temperature. In contrast, trimming did not occur in adcp1Δ strain, wherein the decapping enzyme is lacking. This indicates that trimming is not simply a consequence of the inhibition of mRNA decapping. Third, the temperature-sensitive growth oflsmandpat1mutants was suppressed by mutations in the exosome or the functionally related Ski proteins, which are required for efficient 3′ to 5′ mRNA degradation of mRNA. Moreover, inlsm skidouble mutants, higher levels of the trimmed mRNAs accumulated, indicating that exosome function is not required for mRNA trimming but that the exosome does degrade the trimmed mRNAs. These results raise the possibility that the temperature-sensitive growth of thelsm1-7andpat1mutants is at least partially due to mRNA trimming, which either inactivates the function of the mRNAs or makes them available for premature 3′ to 5′ degradation by the exosome.