Feedback inhibition of poly(A)-binding protein mRNA translation - A possible mechanism of translation arrest by stalled 40 S ribosomal subunits
Feedback inhibition of poly(A)-binding protein mRNA translation - A possible mechanism of translation arrest by stalled 40 S ribosomal subunits
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DOI：
10.1074/jbc.m107676200
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发表时间：
2001-12-14
影响因子：
4.8
通讯作者：
Bag, J
中科院分区：
文献类型：
--
作者：
Bag, J
Pabp 1 mRNA的5 '非翻译区（UTR）富含腺嘌呤的顺式元件能够抑制其自身mRNA的翻译。当将富含腺嘌呤的自动调节序列（ARS）置于报告基因β-半乳糖苷酶mRNA的5 '-UTR内时，观察到该mRNA翻译的类似抑制。对于这种平移控制，ARS与5'帽的距离并不重要。然而，它决定了40 S核糖体亚基的数量结合到的抑制性逮捕的mRNA。该调节序列对mRNA翻译的抑制发生在60 S核糖体亚基与前起始复合物连接的步骤中。在兔网织红细胞裂解物无细胞系统中，在存在外源性Pabp 1的情况下，含有ARS的mRNA的翻译停滞保护ARS的5 '-侧翼区域免受核酸酶消化。这种保护依赖于40 S核糖体亚基与mRNA的结合。核苷酸保护片段的大小和序列取决于ARS在5 '-UTR内的位置。当ARS位于距5'帽约78个核苷酸的距离处时，与ARS相邻的40个核苷酸长的区域被保护。另一方面，当ARS进一步远离5 ′帽移动到类似于267个核苷酸的距离时，与ARS相邻的100个核苷酸长的区域被保护免于核酸酶消化.核酸酶的保护作用是由于在Pabp 1结合的ARS附近存在一个或多个停滞的40 S核糖体亚基。
An adenine-rich cis element at the 5'-untranslated region (UTR) of Pabp1 mRNA is able to inhibit translation of its own mRNA. Similar inhibition of translation of a reporter beta -galactosidase mRNA is observed when the adenine-rich auto regulatory sequence (ARS) is placed within the 5'-UTR of this mRNA. For this translational control the distance of the ARS from the 5' cap is not important. However, it determines the number of 40 S ribosomal subunits bound to the translationally arrested mRNA. Inhibition of mRNA translation by this regulatory sequence occurs at the step of joining of the 60 S ribosomal subunit to the pre-initiation complex. Translational arrest of the ARS containing mRNA in a rabbit reticulocyte lysate cell-free system in the presence of exogenous Pabp1 protects the 5'-flanking region of the ARS from nuclease digestion. This protection depends on the binding of the 40 S ribosomal subunit to the mRNA. The size and the sequence of the nucleotide-protected fragment depends on the location of the ARS within the 5'-UTR. When the ARS is located at a distance of about 78 nucleotides from the 5' cap, a 40-nucleotide-long region adjacent to the ARS is protected. On the other hand, when the ARS is moved further away from the 5' cap to a distance of similar to 267 nucleotides, a 100-nucleotide- long region adjacent to the ARS is protected from nuclease digestion. Nuclease protection is attributed to the presence of one or more stalled 40 S ribosomal subunits near the Pabp1-bound ARS.