Department of Microbiology and Medicine, Howard Hughes Medical Institute, GW Hooper Research Foundation, University of California, San Francisco, CA 94143-0552, USA.
Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5148-53. doi: 10.1073/pnas.1102033108. Epub 2011 Mar 14.
It is widely believed that functional mammalian microRNA (miRNA) recognition sequences are located preferentially in the 3' untranslated region (3'UTR) of target mRNAs. Nonetheless, putative miRNA target sites within coding regions have been found at lower frequency in genome-wide studies, and several have been genetically validated. To account for these findings, it has been proposed that translation may inhibit miRNA access to target sites. Here we identify a naturally occurring viral miRNA target that, owing to the compact nature of the viral transcriptome, is situated naturally in the coding region of one transcript and in the 3'UTR of an overlapping mRNA. Examination of the expression of these mRNAs reveals that the cognate miRNA can inhibit expression in both contexts, but inhibition is more potent when the target site is in the UTR. Similarly, forced translation of the target site in the UTR diminished, but did not abolish, its down-regulation by the miRNA. These data affirm that miRNAs can exert regulatory effects on targets within coding regions; however, the dampening of these effects by translation likely accounts for the observed selection for target sites in the 3'UTRs.
人们普遍认为，功能性哺乳动物 microRNA（miRNA）识别序列优先位于靶 mRNA 的 3'非翻译区（3'UTR）。尽管如此，在全基因组研究中，在编码区中发现了假定的 miRNA 靶位点的频率较低，其中一些已经通过遗传验证。为了解释这些发现，有人提出翻译可能会抑制 miRNA 与靶位点的结合。在这里，我们确定了一个自然发生的病毒 miRNA 靶位，由于病毒转录组的紧凑性质，该靶位自然位于一个转录本的编码区和重叠 mRNA 的 3'UTR 中。检查这些 mRNA 的表达情况表明，同源 miRNA 可以在两种情况下抑制表达，但当靶位位于 UTR 时，抑制作用更强。同样，强制翻译 UTR 中的靶位可降低，但不能消除 miRNA 对其的下调作用。这些数据证实了 miRNA 可以对编码区内的靶标发挥调节作用；然而，翻译对这些作用的抑制可能解释了在 3'UTR 中选择靶位的现象。
