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首页> 外文期刊>Molecular and Cellular Biology >The nonamer UUAUUUAUU is the key AU-rich sequence motif that mediates mRNA degradation.
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The nonamer UUAUUUAUU is the key AU-rich sequence motif that mediates mRNA degradation.

机译：九聚体UUAUUUAUU是介导mRNA降解的富含AU的关键序列基序。

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Labile mRNAs that encode cytokine and immediate-early gene products often contain AU-rich sequences within their 3' untranslated region (UTR). These AU-rich sequences appear to be key determinants of the short half-lives of these mRNAs, although the sequence features of these elements and the mechanism by which they target mRNAs for rapid decay have not been fully defined. We have examined the features of AU-rich elements (AREs) that are crucial for their function as determinants of mRNA instability in mammalian cells by testing the ability of various mutant c-fos AREs and synthetic AREs to direct rapid mRNA deadenylation and decay when inserted within the 3' UTR of the normally stable beta-globin mRNA. Evidence is presented that the pentamer AUUUA, which previously was suggested to be the minimal determinant of instability present in mammalian AREs, cannot direct rapid mRNA deadenylation and decay. Instead, the nonomer UUAUUUAUU is the elemental AU-rich sequence motif that destabilizes mRNA. Removal of one uridine residue from either end of the nonamer (UUAUUUAU or UAUUUAUU) results in a decrease of potency of the element, while removal of a uridine residue from both ends of the nonamer (UAUUUAU) eliminates detectable destabilizing activity. The inclusion of an additional uridine residue at both ends of the nonamer (UUUAUUUAUUU) does not further increase the efficacy of the element. Taken together, these findings suggest that the nonamer UUAUUUAUU is the minimal AU-rich motif that effectively destabilizes mRNA. Additional ARE potency is achieved by combining multiple copies of this nonamer in a single mRNA 3' UTR. Furthermore, analysis of poly(A) shortening rates for ARE-containing mRNAs reveals that the UUAUUUAUU sequence also accelerates mRNA deadenylation and suggests that the UUAUUUAUU motif targets mRNA for rapid deadenylation as an early step in the mRNA decay process.
机译：编码细胞因子和早期基因产物的不稳定mRNA通常在其3'非翻译区（UTR）中包含富含AU的序列。这些富含AU的序列似乎是这些mRNA短半衰期的关键决定因素，尽管尚未完全定义这些元件的序列特征以及它们靶向mRNA进行快速衰变的机制。我们已经通过测试各种突变的c-fos ARE和合成ARE指导快速的mRNA腺苷酸化和插入时衰变的能力，研究了富含AU的元件（ARE）对哺乳动物细胞中mRNA不稳定的决定性至关重要的特征。在正常稳定的β-珠蛋白mRNA的3'UTR中。证据表明，五聚体AUUUA（以前被认为是哺乳动物ARE中不稳定的最小决定因素）不能指导mRNA的快速腺苷酸化和衰变。取而代之的是，非单体UUAUUUAUU是破坏mRNA的富含AU的基本序列基序。从九聚体的任一末端（UUAUUUAU或UAUUUAUU）除去一个尿苷残基会导致元素效力的降低，而从九聚体的两端（UAUUUAU）除去尿苷残基则消除了可检测的去稳定活性。在九聚体（UUUAUUUAUUUU）的两端都包含一个额外的尿苷残基，不会进一步提高该元件的功效。综上所述，这些发现表明，九聚体UUAUUUAUU是有效破坏mRNA的最小化的富含AU的基序。通过在单个mRNA 3'UTR中结合多个该九聚体的拷贝，可以获得额外的ARE效能。此外，对含ARE的mRNA的poly（A）缩短速率的分析显示，UUAUUUAUU序列还加速了mRNA的腺苷酸化，并暗示了UUAUUUAUU基序将mRNA迅速进行腺苷酸化作为mRNA衰变过程的早期步骤。

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