Reichel Marlene, Millar Anthony A
Plant Science Division, Research School of Biology, Australian National University, 2601 ACT, Australia.
Plant Science Division, Research School of Biology, Australian National University, 2601 ACT, Australia.
J Plant Physiol. 2015 May 15;180:45-8. doi: 10.1016/j.jplph.2015.03.010. Epub 2015 Apr 2.
Plant microRNA (miRNA) target MIMICs (MIMs) are non-coding RNA transcripts that can inhibit endogenous miRNAs, as they contain a miRNA binding site that forms a three nucleotide (nt) mismatch loop opposite the miRNA cleavage site upon miRNA binding. This loop renders the MIMs non-cleavable, presumably leading to sequestration of the miRNA and thus enabling the endogenous targets to be deregulated. Arabidopsis miR319 and miR159 are two closely related but distinct miRNA families, as they are functionally specific for two different sets of targets, TCP and MYB genes, respectively. Being offset by one nt, MIM319 and MIM159 should have specificity to their respective miRNA families. However, MIM319 and MIM159 plants appear indistinguishable, having highly similar developmental defects reminiscent of a loss-of-function mir159 mutant. In both MIM319 and MIM159 plants, miR159 and miR319 levels are reduced, and correspondingly, both MYB and TCP mRNA levels are elevated, implying that these MIMs are inhibiting both miR159 and miR319. These data demonstrate that MIMs are able to inhibit closely related miRNAs, including those with cleavage sites not opposite the three nt loop. This highlights that MIMs can have unintended off-target effects and that their use should include corresponding molecular analysis to investigate their impact on closely related miRNAs.
植物微小RNA（miRNA）靶标模拟物（MIM）是非编码RNA转录本，可抑制内源性miRNA，因为它们含有一个miRNA结合位点，在miRNA结合时，该位点会在miRNA切割位点对面形成一个三核苷酸（nt）错配环。这个环使MIM不可切割，推测会导致miRNA被隔离，从而使内源性靶标得以解除调控。拟南芥miR319和miR159是两个密切相关但又不同的miRNA家族，因为它们在功能上分别对两组不同的靶标具有特异性，即TCP基因和MYB基因。由于相差一个nt，MIM319和MIM159应该对各自的miRNA家族具有特异性。然而，MIM319和MIM159植株看起来没有区别，具有高度相似的发育缺陷，让人联想到功能缺失的mir159突变体。在MIM319和MIM159植株中，miR159和miR319的水平都降低了，相应地，MYB和TCP的mRNA水平都升高了，这意味着这些MIM抑制了miR159和miR319。这些数据表明，MIM能够抑制密切相关的miRNA，包括那些切割位点不在三核苷酸环对面的miRNA。这突出表明MIM可能会产生意外的脱靶效应，并且在使用它们时应进行相应的分子分析，以研究它们对密切相关miRNA的影响。
