The 5' terminal oligopyrimidine-tract confers translational control on TOP mRNAs in a cell-type and sequence context-dependent manner
The 5' terminal oligopyrimidine-tract confers translational control on TOP mRNAs in a cell-type and sequence context-dependent manner
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DOI：
10.1093/nar/25.5.995
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发表时间：
1997-03-01
影响因子：
14.9
通讯作者：
Meyuhas, O
中科院分区：
文献类型：
--
作者：
Avni, D;Biberman, Y;Meyuhas, O
Top mRNAs是脊椎动物转录产物，含有5‘末端寡核苷酸(5’top)，编码核糖体蛋白和延伸因子1α和2，是通过其5‘top介导的生长相关翻译调控的候选基因。在本研究中，我们发现延伸因子2(Ef2)在造血来源的细胞中以生长依赖的方式进行翻译调控，但在所研究的三种不同的非造血细胞系中不受调控。人β1-微管蛋白mRNAs是该家族的新成员，它包含了典型top mRNA的所有特征，然而它的翻译对任何被研究的细胞系的生长抑制都是困难的。转染实验表明，编码EF2和β1-微管蛋白的mRNAs的前29个和53个核苷酸分别包含所有的翻译顺式调控元件，足以对报告基因进行普遍的生长依赖的翻译控制；结果表明，顶端mRNAs的不同翻译调节反映了下游序列，这可以以细胞类型特异性的方式覆盖5‘顶端的调节特征。RpS16 mRNA5‘端下游区域的突变进一步支持了这一事实，即rpS16 mRNA5’端下游区域的突变赋予了所产生的转录本生长依赖的翻译控制，其细胞类型特异性类似于EF2mRNA所显示的细胞类型。
TOP mRNAs are vertebrate transcripts which contain a 5' terminal oligopyrimidine tract (5' TOP), encode for ribosomal proteins and elongation factors 1 alpha and 2, and are candidates for growth-dependent translational control mediated through their 5' TOP, In the present study we show that elongation factor 2 (EF2) mRNA is translationally regulated in a growth-dependent manner in cells of hematopoietic origin, but not in any of three different non-hematopoietic cell lines studied, Human beta 1-tubulin mRNA is a new member of the family which contains all the hallmarks of a typical TOP mRNA, yet its translation is refractory to growth arrest of any of the examined cell lines, Transfection experiments indicate that the first 29 and 53 nucleotides of the mRNAs encoding EF2 and beta 1-tubulin, respectively, contain all the translational cis-regulatory elements sufficient for ubiquitously conferring growth-dependent translational control on a reporter mRNA, These; results suggest that the distinct translational regulation of TOP mRNAs reflects downstream sequences which can override the regulatory features of the 5' TOP in a cell type-specific manner. This notion is further supported by the fact that mutations within the region immediately downstream of the 5' TOP of rpS16 mRNA confer onto the resulting transcripts growth-dependent translational control with a cell type specificity similar to that displayed by EF2 mRNA.