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| Open AccessSelfish conflict underlies RNA-mediated parent-of-origin effects
In Caenorhabditis tropicalis, selective expression of genetic alleles from one parent but not the other can arise from maternally inherited small transcripts acting via the PIWI-interacting RNA host defence pathway.
- Pinelopi Pliota
- , Hana Marvanova
- & Alejandro Burga
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Article
| Open AccessRNA-mediated symmetry breaking enables singular olfactory receptor choice
Messenger RNAs transcribed from olfactory-receptor genes may have non-coding functions that include recruitment of transcriptional enhancers and inhibition of potentially thousands of competing alleles to ensure stable transcription of a single allele.
- Ariel D. Pourmorady
- , Elizaveta V. Bashkirova
- & Stavros Lomvardas
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News & Views |
Viruses use RNA decoys to thwart CRISPR defences
Bacteria and archaea are microorganisms that often use RNA-guided defences called CRISPR to destroy the genomes of viruses that infect them. It now emerges that viruses make RNAs that act as mimics to divert such defences.
- Carolyn Kraus
- & Erik J. Sontheimer
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Article
| Open AccessBacteriophages suppress CRISPR–Cas immunity using RNA-based anti-CRISPRs
In response to bacterial CRISPR–Cas immunity, phages and plasmids have evolved small non-coding RNA anti-CRISPRs, known as Racrs, that sequester Cas proteins in abberrant complexes and thereby inhibit immunity.
- Sarah Camara-Wilpert
- , David Mayo-Muñoz
- & Rafael Pinilla-Redondo
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Article
| Open AccesspiRNA processing by a trimeric Schlafen-domain nuclease
The endoribonuclease PUCH, a trimer of Schlafen-like-domain proteins, initiates piRNA processing in the nematode Caenorhabditis elegans through 5′-end piRNA precursor cleavage.
- Nadezda Podvalnaya
- , Alfred W. Bronkhorst
- & René F. Ketting
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Article |
Complementary Alu sequences mediate enhancer–promoter selectivity
Using RNA in situ conformation sequencing technology, the role of Alu elements in mediating the interaction between enhancers and promoters is shown.
- Liang Liang
- , Changchang Cao
- & Yuanchao Xue
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Outlook |
RNA splicing targets age-related diseases
Manipulating genetic molecules could return cells to a younger state.
- Christine Evans-Pughe
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Article
| Open AccessA Pseudomonas aeruginosa small RNA regulates chronic and acute infection
A study examining bacterial gene expression in human-derived samples identifies a gene encoding a small RNA and describes how it orchestrates the transition between chronic and acute infection in Pseudomonas aeruginosa.
- Pengbo Cao
- , Derek Fleming
- & Marvin Whiteley
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News & Views |
MicroRNA uses a gym to get fit for cuts by Dicer enzyme
The enzyme Dicer cleaves a type of RNA called a pre-microRNA to make the mature functional RNA. Structural evidence now sheds light on the catalytic mechanism involved and the role of a newly found RNA sequence termed GYM.
- Gunter Meister
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Article |
Structure of the human DICER–pre-miRNA complex in a dicing state
The active-state structure of human DICER bound to pre-miRNA reveals the structural basis for the specificity of DICER in how it selects substrates in a sequence dependent manner, and sheds light on DICER-related diseases.
- Young-Yoon Lee
- , Hansol Lee
- & Soung-Hun Roh
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Article |
Sequence determinant of small RNA production by DICER
Massively parallel assays reveal a highly conserved sequence motif termed the GYM motif, which potentiates RNA interference by directing Dicer-mediated small RNA processing.
- Young-Yoon Lee
- , Haedong Kim
- & V. Narry Kim
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Article
| Open AccessIn vivo single-molecule analysis reveals COOLAIR RNA structural diversity
The structures of single COOLAIR RNA isoforms change in abundance and shape in response to external conditions; structural mutation of these isoforms altered FLC expression and flowering time, consistent with a regulatory role of the COOLAIR structure in FLC transcription.
- Minglei Yang
- , Pan Zhu
- & Yiliang Ding
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Article |
Selective inhibition of miRNA processing by a herpesvirus-encoded miRNA
Herpesvirus microRNAs interfere directly with host cell microRNA processing, thereby disrupting mitochondrial architecture, evading intrinsic host defences and driving the switch from latent to lytic infection.
- Thomas Hennig
- , Archana B. Prusty
- & Bhupesh K. Prusty
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News & Views |
Phosphorylation found inside RNA
In an impressively thorough study, phosphorylation in the core of a transfer RNA molecule has been described for the first time, and the enzymes that add and remove the phosphate group have been characterized.
- Mark Helm
- & Yuri Motorin
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Article |
Structure of active human telomerase with telomere shelterin protein TPP1
Cryo-electron microscopy structures of human telomerase and telomerase in complex with TPP1 provide insights into the interactions of these proteins and their activities.
- Baocheng Liu
- , Yao He
- & Juli Feigon
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Article |
Targeting Xist with compounds that disrupt RNA structure and X inactivation
A molecule identified in a screen for compounds that bind the non-coding mouse RNA Xist blocks Xist-dependent X-chromosome inactivation, demonstrating the utility of this approach for identifying drugs that target RNA.
- Rodrigo Aguilar
- , Kerrie B. Spencer
- & Jeannie T. Lee
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Article |
MicroRNA sequence codes for small extracellular vesicle release and cellular retention
MicroRNAs encode sorting sequences that determine whether they are secreted in exosomal vesicles to regulate gene expression in distant cells or retained in cells that produced them, with different sequences used by individual cell types.
- Ruben Garcia-Martin
- , Guoxiao Wang
- & C. Ronald Kahn
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Article |
Target site selection and remodelling by type V CRISPR-transposon systems
Structural studies on Scytonema hofmanni CRISPR-associated transposon protein complexes indicate a mechanism for RNA-guided DNA transposition involving Cas12k, TnsC and TnsB.
- Irma Querques
- , Michael Schmitz
- & Martin Jinek
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Article
| Open AccessCold-induced Arabidopsis FRIGIDA nuclear condensates for FLC repression
In Arabidopsis thaliana, downregulation of the floral repressor FLC in response to cold occurs through a mechanism in which the FLC activator FRIGIDA is sequestered into biomolecular condensates away from the FLC promoter.
- Pan Zhu
- , Clare Lister
- & Caroline Dean
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Article |
Structural basis for piRNA targeting
Cryo-electron microscopy structures of a PIWI–piRNA complex provide insight into how piRNAs recognise target RNAs and reveal differences from the target mechanisms of microRNAs.
- Todd A. Anzelon
- , Saikat Chowdhury
- & Ian J. MacRae
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Article |
Shape of promoter antisense RNAs regulates ligand-induced transcription activation
The authors describe a role for the non-coding antisense transcripts produced at promoters in regulating ligand-induced activation of gene transcription.
- Fan Yang
- , Bogdan Tanasa
- & Michael G. Rosenfeld
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Article |
NORAD-induced Pumilio phase separation is required for genome stability
The noncoding RNA NORAD maintains genome stability in mammalian cells by sequestering Pumilio proteins in phase-separated compartments.
- Mahmoud M. Elguindy
- & Joshua T. Mendell
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Article |
MIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration
The natural antisense transcript MAPT-AS1 interferes with translation of mRNA transcript into tau protein in the brain and may represent a general mechanism for controlling levels of intrinsically disordered proteins, with particular relevance for neurodegeneration.
- Roberto Simone
- , Faiza Javad
- & Rohan de Silva
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Article |
Structures of telomerase at several steps of telomere repeat synthesis
Cryo-electron microscopy structures of Tetrahymena telomerase with telomeric DNA at several steps of nucleotide addition provide insights into the structural basis of telomere repeat synthesis.
- Yao He
- , Yaqiang Wang
- & Juli Feigon
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Article |
Global miRNA dosage control of embryonic germ layer specification
The levels of microRNAs in mouse and human cells control lipid metabolism and germ cell specification during development.
- Yingzi Cui
- , Xuehui Lyu
- & Richard I. Gregory
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Article |
Non-coding deletions identify Maenli lncRNA as a limb-specific En1 regulator
The long non-coding RNA locus Maenli controls mouse limb development by regulating En1 activity, and the absence of the homolgous MAENLI locus is associated with severe congenital limb defects in humans.
- Lila Allou
- , Sara Balzano
- & Andrea Superti-Furga
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Article |
RNA nucleation by MSL2 induces selective X chromosome compartmentalization
Dosage compensation in Drosophila involves nucleation of the dosage compensation complex at the X chromosome by MSL2 and the non-coding RNA roX.
- Claudia Isabelle Keller Valsecchi
- , M. Felicia Basilicata
- & Asifa Akhtar
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Article |
RAD51-dependent recruitment of TERRA lncRNA to telomeres through R-loops
Telomeric-repeat-containing RNA is recruited to telomeres by a mechanism that involves the DNA recombinase RAD51 and the formation of DNA–RNA hybrids, or R-loops—a process similar to that involved in homology-directed DNA repair.
- Marianna Feretzaki
- , Michaela Pospisilova
- & Joachim Lingner
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Article |
A protein assembly mediates Xist localization and gene silencing
A protein condensate formed by multivalent interactions between the long non-coding RNA Xist and specific RNA-binding proteins drives the compartmentalization required to perpetuate gene silencing on the inactive X chromosome.
- Amy Pandya-Jones
- , Yolanda Markaki
- & Kathrin Plath
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Article |
Position-specific oxidation of miR-1 encodes cardiac hypertrophy
The 8-oxoguanine modification of the microRNA miR-1 results in redirected recognition and silencing of target genes and leads to cardiac hypertrophy in mice.
- Heeyoung Seok
- , Haejeong Lee
- & Sung Wook Chi
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Article |
Nucleolar RNA polymerase II drives ribosome biogenesis
RNA polymerase II has an unexpected function in the nucleolus, helping to drive the expression of ribosomal RNA and to protect nucleolar structure through a mechanism involving triplex R-loop structures.
- Karan J. Abraham
- , Negin Khosraviani
- & Karim Mekhail
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Article |
poly(UG)-tailed RNAs in genome protection and epigenetic inheritance
In Caenorhabditis elegans, the ribonucleotidyltransferase RDE-3 adds alternating uridine and guanosine ribonucleotides to the 3′ termini of RNAs, a key step in RNA interference and thus epigenetic inheritance in the C. elegans germline.
- Aditi Shukla
- , Jenny Yan
- & Scott Kennedy
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Article |
RIC-seq for global in situ profiling of RNA–RNA spatial interactions
RNA in situ conformation sequencing (RIC-seq) enables the generation of three-dimensional interaction maps of RNA in cells, which sheds light on the interactions and regulatory functions of RNA.
- Zhaokui Cai
- , Changchang Cao
- & Yuanchao Xue
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Article |
A satellite repeat-derived piRNA controls embryonic development of Aedes
A conserved satellite repeat in the mosquito Aedes aegypti encodes PIWI-interacting RNAs that promote sequence-specific gene silencing in trans and have an essential role in embryonic development.
- Rebecca Halbach
- , Pascal Miesen
- & Ronald P. van Rij
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Article |
U1 snRNP regulates chromatin retention of noncoding RNAs
Long noncoding RNAs and certain unstable transcripts tend to localize to chromatin, in a process that is shown here to depend on an RNA motif that recognizes the small nuclear ribonuclear protein U1, and to rely on transcription.
- Yafei Yin
- , J. Yuyang Lu
- & Xiaohua Shen
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News & Views |
DNA-repair enzyme turns to translation
A key DNA-repair enzyme has a surprising role during the early steps in the assembly of ribosomes — the molecular machines that translate the genetic code into protein.
- Alan J. Warren
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Article |
DNA-PKcs has KU-dependent function in rRNA processing and haematopoiesis
The catalytic subunit of DNA-PK autophosphorylates and contributes to ribosome biogenesis and haematopoiesis by binding to the U3 small nucleolar RNA.
- Zhengping Shao
- , Ryan A. Flynn
- & Eliezer Calo
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News & Views |
How to silence an X chromosome
The non-coding RNA Xist has been shown to enlist the SPEN protein to recruit a team of protein complexes — initiating the process that prevents transcription of one of the two X chromosomes found in female mammalian cells.
- Jackson B. Trotman
- & J. Mauro Calabrese
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Article |
SPEN integrates transcriptional and epigenetic control of X-inactivation
The transcriptional repressor SPEN bridges the non-coding RNA Xist to transcription machinery, histone deacetylases and chromatin remodelling factors to initiate X-chromosome inactivation.
- François Dossin
- , Inês Pinheiro
- & Edith Heard
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Article |
Zucchini consensus motifs determine the mechanism of pre-piRNA production
A silkworm model recapitulates key steps of Zucchini-mediated cleavage of pre-pre-piRNA and provides insights into Zucchini-mediated and -independent pathways that generate pre-piRNAs, which converge to a common piRNA maturation step.
- Natsuko Izumi
- , Keisuke Shoji
- & Yukihide Tomari
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Article |
The molecular landscape of ETMR at diagnosis and relapse
Analyses of primary and relapse samples of embryonal tumours with multilayered rosettes provide insights into the molecular mechanisms that underlie the development and opportunities for the treatment of this deadly disease.
- Sander Lambo
- , Susanne N. Gröbner
- & Marcel Kool
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Outlook |
How RNA therapies could be used to tackle the world’s biggest killer
Researchers hope that understanding the many roles of non-coding RNA in heart health and cardiovascular disease could deliver a therapeutic breakthrough.
- Chris Woolston
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Outlook |
The challenge of delivering RNA-interference therapeutics to their target cells
Delivery difficulties brought the nascent research field to its knees, but approval of the first RNA interference drug offers hope.
- Bianca Nogrady
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Article |
Developmental dynamics of lncRNAs across mammalian organs and species
A transcriptome dataset from seven organs and seven mammalian species throughout development is used to analyse the expression of long noncoding RNAs in tissues within and between species, and at different stages of organ development.
- Ioannis Sarropoulos
- , Ray Marin
- & Henrik Kaessmann
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Letter |
MicroRNA therapy stimulates uncontrolled cardiac repair after myocardial infarction in pigs
MicroRNAs delivered by adeno-associated viral vectors improve global and regional contractility, increase muscle mass and reduce scar size in a porcine model of myocardial infarction.
- Khatia Gabisonia
- , Giulia Prosdocimo
- & Mauro Giacca
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Letter |
Arabidopsis FLL2 promotes liquid–liquid phase separation of polyadenylation complexes
A genetic screen for factors required by the Arabidopsis RNA-binding protein FCA identifies FLL2 as necessary in the formation of FCA nuclear bodies, and thus a role for FLL2 in liquid–liquid phase separation.
- Xiaofeng Fang
- , Liang Wang
- & Caroline Dean
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News & Views |
Genetic paradox explained by nonsense
Gene mutations that truncate the encoded protein can trigger the expression of related genes. The discovery of this compensatory response changes how we think about genetic studies in humans and model organisms.
- Miles F. Wilkinson
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Article |
Genetic compensation triggered by mutant mRNA degradation
Transcriptional adaptation, a genetic compensation process by which organisms respond to mutations by upregulating related genes, is triggered by mRNA decay and involves a sequence-dependent mechanism.
- Mohamed A. El-Brolosy
- , Zacharias Kontarakis
- & Didier Y. R. Stainier
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News & Views |
Intron RNA sequences help yeast cells to survive starvation
Intron sequences are removed from newly synthesized RNA and usually rapidly degraded. However, it now seems that introns have a surprising role — helping yeast cells survive when nutrients are scarce.
- Samantha R. Edwards
- & Tracy L. Johnson