Target mimicry provides a new mechanism for regulation of microRNA activity

Abstract

MicroRNAs (miRNA) regulate key aspects of development and physiology in animals and plants. These regulatory RNAs act as guides of effector complexes to recognize specific mRNA sequences based on sequence complementarity, resulting in translational repression or site-specific cleavage. In plants, most miRNA targets are cleaved and show almost perfect complementarity with the miRNAs around the cleavage site. Here, we examined the non-protein coding gene IPS1 (INDUCED BY PHOSPHATE STARVATION 1) from Arabidopsis thaliana. IPS1 contains a motif with sequence complementarity to the phosphate (Pi) starvation-induced miRNA miR-399, but the pairing is interrupted by a mismatched loop at the expected miRNA cleavage site. We show that IPS1 RNA is not cleaved but instead sequesters miR-399. Thus, IPS1 overexpression results in increased accumulation of the miR-399 target PHO2 mRNA and, concomitantly, in reduced shoot Pi content. Engineering of IPS1 to be cleavable abolishes its inhibitory activity on miR-399. We coin the term 'target mimicry' to define this mechanism of inhibition of miRNA activity. Target mimicry can be generalized beyond the control of Pi homeostasis, as demonstrated using artificial target mimics.

Extensive microRNA-mediated crosstalk between lncRNAs and mRNAs in mouse embryonic stem cells

“…Not only have most lnceRNAs been described in the context of this critical cellular transition but their impact on gene expression profiles, when pools of miRNAs are limited and changes in their repertoires can lead to repression or activation of transcriptional programs, is likely to be greater than in fully differentiated cells or in homeostasis. Environmental or cellular stress, for example upon starvation or infection (Ebert et al 2007;Franco-Zorrilla et al 2007), may also offer similar opportunities for strong effects of small changes in target gene expression.…”

“…The miRNA-mediated crosstalk among transcripts can involve coding as well as noncoding transcripts, including intergenic long noncoding RNAs (lncRNAs) (Franco-Zorrilla et al 2007;Cesana et al 2011;Wang et al 2013). Thousands of lncRNAs have been annotated in eukaryotic genomes (Derrien et al 2012;Ulitsky and Bartel 2013), many of which are preferentially located in the cytoplasm (van Heesch et al 2014), where they can engage in miRNA-mediated interactions with other transcripts.…”

MicroRNAs in tomato plants

“…There are several approaches to study the functions of miRNAs, such as overexpression of the target miRNAs, expression of mutant target genes [9,76], and expression of miRNA target mimicries [77], and these methods are usually tedious and time consuming for generation of stable transgenic plants. Surprisingly, a viral miRNA expression system could be used to study the function of endogenous miRNA genes by agro-infiltration in Nicotiana benthamiana plants [78].…”

A stable tRNA-like molecule is generated from the long noncoding RNA GUT15 in Arabidopsis

“…In addition, plant lncRNAs have been associated with other biological processes. Phosphate homeostasis is regulated by the IPS1 lncRNA, which acts as an endogenous target mimic of miR399 [9]. Photomorphogenesis in Arabidopsis seedlings is regulated by the HID3 lncRNA, which is known to associate with PIF3 locus chromatin and repress its transcription [10].…”