Ribosome profiling shows that miR-430 reduces translation before causing mRNA decay in zebrafish.

Ribosome profiling shows that miR-430 reduces translation before causing mRNA decay in zebrafish.
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DOI:
10.1126/science.1215704
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发表时间:
2012-04-13
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Giraldez AJ
Giraldez AJ
中科院分区:
其他
文献类型:
--
作者:
Bazzini AA;Lee MT;Giraldez AJ

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microRNA通过去腺苷化、阻遏和mRNA降解来调节基因表达。然而,每种机制在非稳态情况下的贡献仍不清楚。我们监测了miR-430对缺乏成熟miR-430的野生型和dicer突变体中内源性mRNA的核糖体占据的影响。我们发现miR-430在导致mRNA衰变之前减少了靶mRNA上的核糖体数量。翻译阻遏发生在完全去腺苷化之前,并且使用内部聚腺苷酸尾破坏去腺苷化并不阻断靶阻遏。最后,我们观察到核糖体密度沿着信息的长度保持恒定,这表明翻译抑制是通过降低起始速率而不是影响延伸或引起核糖体脱落而发生的。总之,我们的结果表明,miR-430在诱导mRNA降解之前调节翻译起始。
MicroRNAs regulate gene expression through deadenylation, repression and mRNA decay. However, the contribution of each mechanism in non-steady-state situations remains unclear. We monitored the impact of miR-430 on ribosome occupancy of endogenous mRNAs in wild type and dicer mutants lacking mature miR-430. We find that miR-430 reduces the number of ribosomes on target mRNAs before causing mRNA decay. Translational repression occurs before complete deadenylation, and disrupting deadenylation using an internal poly(A) tail did not block target repression. Finally, we observe that ribosome density along the length of the message remains constant, suggesting that translational repression occurs by reducing the rate of initiation rather than affecting elongation or causing ribosomal drop-off. In summary, our results show that miR-430 regulates translation initiation before inducing mRNA decay.
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