Translational control elements in the major human transforming growth factor-β1 mRNA
Translational control elements in the major human transforming growth factor-β1 mRNA
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DOI：
10.3109/08977199809002120
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发表时间：
1998-01-01
期刊：
影响因子：
1.8
通讯作者：
Wakefield, LM
中科院分区：
文献类型：
--
作者：
Allison, RSH;Mumy, ML;Wakefield, LM
多核糖体分析表明，主要的2.4 kb的转化生长因子-β 1（TGF-β 1）的转录是很差的翻译，无论是在培养的细胞，并在体内小鼠肝脏。通过缺失分析研究了5 '-和3'-非翻译区（UTR）对全长TGF-β 1转录本的翻译抑制作用。尽管它们的G+C含量很高，但这两个UTR在葡萄中都能促进翻译。然而，转染入MCF-7细胞的合成TGF-β 1 mRNA的多核糖体分析表明，该细胞含有有限的反式作用因子库，这些因子与5 ′-UTR相互作用，使其在体内具有抑制性。体外进一步缺失分析揭示了5 ′-UTR中的多个刺激和抑制区域，这对自然发生的较短的TGF-β 1转录本的可翻译性具有重要意义，并为更高分辨率的定位研究提供了框架。总体而言，体内主要TGF-β 1 mRNA的翻译效率差似乎是由于起始序列背景差以及限制性反式作用因子与嵌入在刺激性5 'UTR中的顺式抑制元件的抑制性相互作用的组合。
Polysome analysis indicates that the major 2.4 kb transforming growth factor-beta 1 (TGF-beta 1) transcript is poorly translated, both in cultured cells, and in vivo in mouse liver. In contrast, the TGF-beta 2 transcripts are efficiently translated, The contribution of the 5'- and 3'-untranslated regions (UTRs) to the translational inhibition of the full-length TGF-beta 1 transcript was studied by deletion analysis, Despite their high G+C content, both UTRs stimulated translation in vine. However, polysome analysis of synthetic TGF-beta 1 mRNAs transfected into MCF-7 cells suggests that the cell contains a limited pool of trans-acting factors that interact with the 5'-UTR to make it inhibitory in viva, Further deletion analysis in vitro revealed multiple stimulatory and inhibitory regions in the 5'UTR, This has important implications for the translatability of the naturally occurring shorter TGF-beta 1 transcripts and provides a framework for higher resolution mapping studies. Overall, the poor translational efficiency of the major TGF-beta 1 mRNA in vivo appears to be due to a combination of poor initiation sequence context, and inhibitory interactions of limiting transacting factors with cis-inhibitory elements embedded in an otherwise stimulatory 5'UTR.