scispace - formally typeset
Search or ask a question
Author

Javier Paz-Ares

Bio: Javier Paz-Ares is an academic researcher from Spanish National Research Council. The author has contributed to research in topics: Arabidopsis & Gene. The author has an hindex of 45, co-authored 74 publications receiving 12178 citations. Previous affiliations of Javier Paz-Ares include Autonomous University of Madrid & Polytechnic University of Puerto Rico.


Papers
More filters
Journal ArticleDOI
TL;DR: Target mimicry can be generalized beyond the control of Pi homeostasis, as demonstrated using artificial target mimics and coined to define this mechanism of inhibition of miRNA 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.

1,767 citations

Journal ArticleDOI
TL;DR: PHR1-binding sequences are present in the promoter of Pi starvation-responsive structural genes, indicating that this protein acts downstream in the Pi starvation signaling pathway.
Abstract: Plants have evolved a number of adaptive responses to cope with growth in conditions of limited phosphate (Pi) supply involving biochemical, metabolic, and developmental changes. We prepared an EMS-mutagenized M(2) population of an Arabidopsis thaliana transgenic line harboring a reporter gene specifically responsive to Pi starvation (AtIPS1::GUS), and screened for mutants altered in Pi starvation regulation. One of the mutants, phr1 (phosphate starvation response 1), displayed reduced response of AtIPS1::GUS to Pi starvation, and also had a broad range of Pi starvation responses impaired, including the responsiveness of various other Pi starvation-induced genes and metabolic responses, such as the increase in anthocyanin accumulation. PHR1 was positionally cloned and shown be related to the PHOSPHORUS STARVATION RESPONSE 1 (PSR1) gene from Chlamydomonas reinhardtii. A GFP::PHR1 protein fusion was localized in the nucleus independently of Pi status, as is the case for PSR1. PHR1 is expressed in Pi sufficient conditions and, in contrast to PSR1, is only weakly responsive to Pi starvation. PHR1, PSR1, and other members of the protein family share a MYB domain and a predicted coiled-coil (CC) domain, defining a subtype within the MYB superfamily, the MYB-CC family. Therefore, PHR1 was found to bind as a dimer to an imperfect palindromic sequence. PHR1-binding sequences are present in the promoter of Pi starvation-responsive structural genes, indicating that this protein acts downstream in the Pi starvation signaling pathway.

1,103 citations

Journal ArticleDOI
TL;DR: The results show that MYC3 and MYC4 are activators of JA-regulated programs that act additively with MYC2 to regulate specifically different subsets of the JA-dependent transcriptional response.
Abstract: Jasmonates (JAs) trigger an important transcriptional reprogramming of plant cells to modulate both basal development and stress responses. In spite of the importance of transcriptional regulation, only one transcription factor (TF), the Arabidopsis thaliana basic helix-loop-helix MYC2, has been described so far as a direct target of JAZ repressors. By means of yeast two-hybrid screening and tandem affinity purification strategies, we identified two previously unknown targets of JAZ repressors, the TFs MYC3 and MYC4, phylogenetically closely related to MYC2. We show that MYC3 and MYC4 interact in vitro and in vivo with JAZ repressors and also form homo- and heterodimers with MYC2 and among themselves. They both are nuclear proteins that bind DNA with sequence specificity similar to that of MYC2. Loss-of-function mutations in any of these two TFs impair full responsiveness to JA and enhance the JA insensitivity of myc2 mutants. Moreover, the triple mutant myc2 myc3 myc4 is as impaired as coi1-1 in the activation of several, but not all, JA-mediated responses such as the defense against bacterial pathogens and insect herbivory. Our results show that MYC3 and MYC4 are activators of JA-regulated programs that act additively with MYC2 to regulate specifically different subsets of the JA-dependent transcriptional response.

896 citations

Journal ArticleDOI
Javier Paz-Ares1, D. Ghosal1, Udo Wienand1, P A Peterson1, Heinz Saedler1 
TL;DR: The structure of the wild‐type c1 locus of Zea mays was determined by sequence analysis of one genomic and two cDNA clones by deducing a putative protein, 273 amino acids in length, which contains two domains, one basic and the other acidic and might function as a transcriptional activator.
Abstract: The structure of the wild-type c1 locus of Zea mays was determined by sequence analysis of one genomic and two cDNA clones. The coding region is composed of three exons (150 bp, 129 bp and one, at least 720 bp) and two small introns (88 bp and 145 bp). Transcription of the mRNAs corresponding to the two cDNA clones cLC6 (1.1 kb) and cLC28 (2.1 kb) starts from the same promoter. Both cDNAs are identical except that cLC28 extends further at its 3' end. A putative protein, 273 amino acids in length was deduced from the sequence of both transcripts. It contains two domains, one basic and the other acidic and might function as a transcriptional activator. The basic domain of this c1-encoded protein shows 40% sequence homology to the protein products of animal myb proto-oncogenes.

848 citations

Journal ArticleDOI
TL;DR: In vertebrates, the MYB-related proto-oncogenes comprise a small family with a central role in controlling cellular proliferation and commitment to development, but while the functions of some plant MYB genes are relatively well understood they are, at present, quite distinct from their animal counterparts.

576 citations


Cited by
More filters
Journal ArticleDOI
21 Mar 2013-Nature
TL;DR: It is found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7.
Abstract: Circular RNAs (circRNAs) in animals are an enigmatic class of RNA with unknown function. To explore circRNAs systematically, we sequenced and computationally analysed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, often showing tissue/developmental-stage-specific expression. Sequence analysis indicated important regulatory functions for circRNAs. We found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebrafish impaired midbrain development, similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA-binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, suggesting previously unrecognized regulatory potential of coding sequences.

5,922 citations

Journal ArticleDOI
21 Mar 2013-Nature
TL;DR: This study serves as the first functional analysis of a naturally expressed circular RNA, ciRS-7, which contains more than 70 selectively conserved miRNA target sites, and is highly and widely associated with Argonaute proteins in a miR-7-dependent manner.
Abstract: MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants. We previously identified a highly expressed circular RNA (circRNA) in human and mouse brain. Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ciRS-7 contains more than 70 selectively conserved miRNA target sites, and it is highly and widely associated with Argonaute (AGO) proteins in a miR-7-dependent manner. Although the circRNA is completely resistant to miRNA-mediated target destabilization, it strongly suppresses miR-7 activity, resulting in increased levels of miR-7 targets. In the mouse brain, we observe overlapping co-expression of ciRS-7 and miR-7, particularly in neocortical and hippocampal neurons, suggesting a high degree of endogenous interaction. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. This study serves as the first, to our knowledge, functional analysis of a naturally expressed circRNA.

5,885 citations

Journal ArticleDOI
05 Aug 2011-Cell
TL;DR: It is proposed that this "competing endogenous RNA" (ceRNA) activity forms a large-scale regulatory network across the transcriptome, greatly expanding the functional genetic information in the human genome and playing important roles in pathological conditions, such as cancer.

5,334 citations

01 Jan 2007

4,037 citations

Journal ArticleDOI
TL;DR: These archetypes of lncRNA function may be a useful framework to consider how lncRNAs acquire properties as biological signal transducers and hint at their possible origins in evolution.

3,621 citations