MicroRNAs Cause Accelerated Decay of Short-Tailed Target mRNAs
MicroRNAs Cause Accelerated Decay of Short-Tailed Target mRNAs
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DOI：
10.1016/j.molcel.2019.12.004
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发表时间：
2020-02-20
期刊：
影响因子：
16
通讯作者：
Bartel, David P.
中科院分区：
文献类型：
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作者：
Eisen, Timothy J.;Eichhorn, Stephen W.;Bartel, David P.
microRNA（miRNAs）指定腺苷酸化酶向mRNA靶标的募集。尽管有这种招募，我们发现miRNA对其靶点在小鼠成纤维细胞中的稳态poly（A）尾长度几乎没有影响，这激发了对miRNA对尾长、mRNA影响的稳态前测量的获取水平和翻译效率。与对mRNA水平的影响相比，对翻译效率的影响最小，即使是新转录的靶mRNA。对靶mRNA水平的影响随着mRNA群体接近稳态而累积，而对最近转录的靶mRNA的尾长的影响达到峰值，然后消退。对这一现象的计算建模表明，miRNA不仅导致其靶分子的加速去腺苷化，而且还导致短尾靶分子的加速衰变。尽管加速了靶去腺苷化，但miRNA的这种意想不到的作用在很大程度上阻止了短尾靶mRNA的积累。最终结果是靶向mRNA的稳态尾长分布发生了几乎察觉不到的变化。
MicroRNAs (miRNAs) specify the recruitment of deadenylases to mRNA targets. Despite this recruitment, we find that miRNAs have almost no effect on steady-state poly(A)-tail lengths of their targets in mouse fibroblasts, which motivates the acquisition of pre-steady-state measurements of the effects of miRNAs on tail lengths, mRNA levels, and translational efficiencies. Effects on translational efficiency are minimal compared to effects on mRNA levels, even for newly transcribed target mRNAs. Effects on target mRNA levels accumulate as the mRNA population approaches steady state, whereas effects on tail lengths peak for recently transcribed target mRNAs and then subside. Computational modeling of this phenomenon reveals that miRNAs cause not only accelerated deadenylation of their targets but also accelerated decay of short-tailed target molecules. This unanticipated effect of miRNAs largely prevents short-tailed target mRNAs from accumulating despite accelerated target deadenylation. The net result is a nearly imperceptible change to the steady-state tail-length distribution of targeted mRNAs.