Journal ArticleDOI
Target mimicry provides a new mechanism for regulation of microRNA activity
José Manuel Franco-Zorrilla,Adrian Valli,Marco Todesco,I. Mateos,María Isabel Puga,Ignacio Rubio-Somoza,Antonio Leyva,Detlef Weigel,Juan Antonio García,Javier Paz-Ares +9 more
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TLDR
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.read more
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Journal ArticleDOI
Circular RNAs are a large class of animal RNAs with regulatory potency
Sebastian Memczak,Marvin Jens,Antigoni Elefsinioti,Francesca Torti,Janna Krueger,Agnieszka Rybak,Luisa Maier,Sebastian D. Mackowiak,Lea H. Gregersen,Mathias Munschauer,Alexander Loewer,Ulrike Ziebold,Markus Landthaler,Christine Kocks,Ferdinand le Noble,Nikolaus Rajewsky +15 more
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.
Journal ArticleDOI
Natural RNA circles function as efficient microRNA sponges
Thomas B. Hansen,Trine I. Jensen,Bettina Hjelm Clausen,Jesper B. Bramsen,Bente Finsen,Christian Kroun Damgaard,Jørgen Kjems +6 more
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.
Journal ArticleDOI
A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?
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.
Journal ArticleDOI
Molecular Mechanisms of Long Noncoding RNAs
Kevin C. Wang,Howard Y. Chang +1 more
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.
Journal ArticleDOI
starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data
TL;DR: This study developed starBase v2.0, which has been updated to provide the most comprehensive CLIP-Seq experimentally supported miRNA-mRNA and mi RNA-lncRNA interaction networks to date, and developed miRFunction and ceRNAFunction web servers to predict the function of miRNAs and other ncRNAs from themiRNA-mediated regulatory networks.
References
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Journal ArticleDOI
MicroRNAs: Genomics, Biogenesis, Mechanism, and Function
TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
Journal ArticleDOI
MicroRNAs: small RNAs with a big role in gene regulation
Lin He,Gregory J. Hannon +1 more
TL;DR: Two founding members of the microRNA family were originally identified in Caenorhabditis elegans as genes that were required for the timed regulation of developmental events and indicate the existence of multiple RISCs that carry out related but specific biological functions.
Book ChapterDOI
Assay of inorganic phosphate, total phosphate and phosphatase
TL;DR: The method is about seven times as sensitive as the Fiske–SubbaRow procedure and involves less pipetting, but it is not very satisfactory for determining inorganic phosphate if labile phosphate esters are present in large excess.
Journal ArticleDOI
MicroRNAs AND THEIR REGULATORY ROLES IN PLANTS
TL;DR: The importance of miRNA-directed gene regulation during plant development is now particularly clear and typically at the cores of gene regulatory networks, targeting genes that are themselves regulators, such as those encoding transcription factors and F-box proteins.
Journal ArticleDOI
Correction: MicroRNAs: small RNAs with a big role in gene regulation
Lin He,Gregory J. Hannon +1 more
TL;DR: A large number of microRNAs have been identified in almost all metazoan genomes, including worms, flies, plants and mammals, and their discovery adds a new dimension to the understanding of complex gene regulatory networks.