Howard Hughes Medical Institute and Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA;
Genome Res. 2013 Dec;23(12):2078-90. doi: 10.1101/gr.156919.113. Epub 2013 Sep 26.
Variation in protein output across the genome is controlled at several levels, but the relative contributions of different regulatory mechanisms remain poorly understood. Here, we obtained global measurements of decay and translation rates for mRNAs with alternative 3' untranslated regions (3' UTRs) in murine 3T3 cells. Distal tandem isoforms had slightly but significantly lower mRNA stability and greater translational efficiency than proximal isoforms on average. The diversity of alternative 3' UTRs also enabled inference and evaluation of both positively and negatively acting cis-regulatory elements. The 3' UTR elements with the greatest implied influence were microRNA complementary sites, which were associated with repression of 32% and 4% at the stability and translational levels, respectively. Nonetheless, both the decay and translation rates were highly correlated for proximal and distal 3' UTR isoforms from the same genes, implying that in 3T3 cells, alternative 3' UTR sequences play a surprisingly small regulatory role compared to other mRNA regions.
基因组中蛋白质输出的变化是在几个层面上控制的，但不同调节机制的相对贡献仍知之甚少。在这里，我们在鼠 3T3 细胞中获得了具有不同 3' 非翻译区（3'UTR）的 mRNA 降解和翻译速率的全局测量值。平均而言，远端串联异构体的 mRNA 稳定性略低，但翻译效率明显更高。不同的 3'UTR 还能够推断和评估正向和负向的顺式调节元件。具有最大暗示影响的 3'UTR 元件是 microRNA 互补位点，它们分别与稳定性和翻译水平上的 32%和 4%的抑制作用相关。尽管如此，来自同一基因的近端和远端 3'UTR 异构体的降解和翻译速率都高度相关，这意味着在 3T3 细胞中，与其他 mRNA 区域相比，替代 3'UTR 序列的调节作用惊人地小。
