Publications by authors named "Noa Gil"

9 Publications

  • Page 1 of 1

Regulation of neuronal commitment in mouse embryonic stem cells by the Reno1/Bahcc1 locus.

EMBO Rep 2020 11 24;21(11):e51264. Epub 2020 Sep 24.

Weizmann Institute of Science, Rehovot, Israel.

Mammalian genomes encode thousands of long noncoding RNAs (lncRNAs), yet the biological functions of most of them remain unknown. A particularly rich repertoire of lncRNAs found in mammalian brain and in the early embryo. We used RNA-seq and computational analysis to prioritize lncRNAs that may regulate commitment of pluripotent cells to a neuronal fate and perturbed their expression prior to neuronal differentiation. Knockdown by RNAi of two highly conserved and well-expressed lncRNAs, Reno1 (2810410L24Rik) and lnc-Nr2f1, decreased the expression of neuronal markers and led to massive changes in gene expression in the differentiated cells. We further show that the Reno1 locus forms increasing spatial contacts during neurogenesis with its adjacent protein-coding gene Bahcc1. Loss of either Reno1 or Bahcc1 leads to an early arrest in neuronal commitment, failure to induce a neuronal gene expression program, and to global reduction in chromatin accessibility at regions that are marked by the H3K4me3 chromatin mark at the onset of differentiation. Reno1 and Bahcc1 thus form a previously uncharacterized circuit required for the early steps of neuronal commitment.
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http://dx.doi.org/10.15252/embr.202051264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645239PMC
November 2020

Functional annotation of human long noncoding RNAs via molecular phenotyping.

Authors:
Jordan A Ramilowski Chi Wai Yip Saumya Agrawal Jen-Chien Chang Yari Ciani Ivan V Kulakovskiy Mickaël Mendez Jasmine Li Ching Ooi John F Ouyang Nick Parkinson Andreas Petri Leonie Roos Jessica Severin Kayoko Yasuzawa Imad Abugessaisa Altuna Akalin Ivan V Antonov Erik Arner Alessandro Bonetti Hidemasa Bono Beatrice Borsari Frank Brombacher Christopher JF Cameron Carlo Vittorio Cannistraci Ryan Cardenas Melissa Cardon Howard Chang Josée Dostie Luca Ducoli Alexander Favorov Alexandre Fort Diego Garrido Noa Gil Juliette Gimenez Reto Guler Lusy Handoko Jayson Harshbarger Akira Hasegawa Yuki Hasegawa Kosuke Hashimoto Norihito Hayatsu Peter Heutink Tetsuro Hirose Eddie L Imada Masayoshi Itoh Bogumil Kaczkowski Aditi Kanhere Emily Kawabata Hideya Kawaji Tsugumi Kawashima S Thomas Kelly Miki Kojima Naoto Kondo Haruhiko Koseki Tsukasa Kouno Anton Kratz Mariola Kurowska-Stolarska Andrew Tae Jun Kwon Jeffrey Leek Andreas Lennartsson Marina Lizio Fernando López-Redondo Joachim Luginbühl Shiori Maeda Vsevolod J Makeev Luigi Marchionni Yulia A Medvedeva Aki Minoda Ferenc Müller Manuel Muñoz-Aguirre Mitsuyoshi Murata Hiromi Nishiyori Kazuhiro R Nitta Shuhei Noguchi Yukihiko Noro Ramil Nurtdinov Yasushi Okazaki Valerio Orlando Denis Paquette Callum J C Parr Owen J L Rackham Patrizia Rizzu Diego Fernando Sánchez Martinez Albin Sandelin Pillay Sanjana Colin A M Semple Youtaro Shibayama Divya M Sivaraman Takahiro Suzuki Suzannah C Szumowski Michihira Tagami Martin S Taylor Chikashi Terao Malte Thodberg Supat Thongjuea Vidisha Tripathi Igor Ulitsky Roberto Verardo Ilya E Vorontsov Chinatsu Yamamoto Robert S Young J Kenneth Baillie Alistair R R Forrest Roderic Guigó Michael M Hoffman Chung Chau Hon Takeya Kasukawa Sakari Kauppinen Juha Kere Boris Lenhard Claudio Schneider Harukazu Suzuki Ken Yagi Michiel J L de Hoon Jay W Shin Piero Carninci

Genome Res 2020 07 27;30(7):1060-1072. Epub 2020 Jul 27.

RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.

Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-to-date lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for and .
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http://dx.doi.org/10.1101/gr.254219.119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397864PMC
July 2020

Author Correction: In-cell identification and measurement of RNA-protein interactions.

Nat Commun 2020 07 8;11(1):3498. Epub 2020 Jul 8.

Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, Paris, 75005, France.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41467-020-17282-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343817PMC
July 2020

In-cell identification and measurement of RNA-protein interactions.

Nat Commun 2019 11 22;10(1):5317. Epub 2019 Nov 22.

Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, Paris, 75005, France.

Regulatory RNAs exert their cellular functions through RNA-binding proteins (RBPs). Identifying RNA-protein interactions is therefore key for a molecular understanding of regulatory RNAs. To date, RNA-bound proteins have been identified primarily through RNA purification followed by mass spectrometry. Here, we develop incPRINT (in cell protein-RNA interaction), a high-throughput method to identify in-cell RNA-protein interactions revealed by quantifiable luminescence. Applying incPRINT to long noncoding RNAs (lncRNAs), we identify RBPs specifically interacting with the lncRNA Firre and three functionally distinct regions of the lncRNA Xist. incPRINT confirms previously known lncRNA-protein interactions and identifies additional interactions that had evaded detection with other approaches. Importantly, the majority of the incPRINT-defined interactions are specific to individual functional regions of the large Xist transcript. Thus, we present an RNA-centric method that enables reliable identification of RNA-region-specific RBPs and is applicable to any RNA of interest.
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http://dx.doi.org/10.1038/s41467-019-13235-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876571PMC
November 2019

Regulation of gene expression by cis-acting long non-coding RNAs.

Nat Rev Genet 2020 02 15;21(2):102-117. Epub 2019 Nov 15.

Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.

Long non-coding RNAs (lncRNAs) are diverse transcription products emanating from thousands of loci in mammalian genomes. Cis-acting lncRNAs, which constitute a substantial fraction of lncRNAs with an attributed function, regulate gene expression in a manner dependent on the location of their own sites of transcription, at varying distances from their targets in the linear genome. Through various mechanisms, cis-acting lncRNAs have been demonstrated to activate, repress or otherwise modulate the expression of target genes. We discuss the activities that have been ascribed to cis-acting lncRNAs, the evidence and hypotheses regarding their modes of action, and the methodological advances that enable their identification and characterization. The emerging principles highlight lncRNAs as transcriptional units highly adept at contributing to gene regulatory networks and to the generation of fine-tuned spatial and temporal gene expression programmes.
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http://dx.doi.org/10.1038/s41576-019-0184-5DOI Listing
February 2020

Regulation of CHD2 expression by the Chaserr long noncoding RNA gene is essential for viability.

Nat Commun 2019 11 8;10(1):5092. Epub 2019 Nov 8.

Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.

Chromodomain helicase DNA binding protein 2 (Chd2) is a chromatin remodeller implicated in neurological disease. Here we show that Chaserr, a highly conserved long noncoding RNA transcribed from a region near the transcription start site of Chd2 and on the same strand, acts in concert with the CHD2 protein to maintain proper Chd2 expression levels. Loss of Chaserr in mice leads to early postnatal lethality in homozygous mice, and severe growth retardation in heterozygotes. Mechanistically, loss of Chaserr leads to substantially increased Chd2 mRNA and protein levels, which in turn lead to transcriptional interference by inhibiting promoters found downstream of highly expressed genes. We further show that Chaserr production represses Chd2 expression solely in cis, and that the phenotypic consequences of Chaserr loss are rescued when Chd2 is perturbed as well. Targeting Chaserr is thus a potential strategy for increasing CHD2 levels in haploinsufficient individuals.
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http://dx.doi.org/10.1038/s41467-019-13075-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6841665PMC
November 2019

Production of Spliced Long Noncoding RNAs Specifies Regions with Increased Enhancer Activity.

Cell Syst 2018 11 14;7(5):537-547.e3. Epub 2018 Nov 14.

Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address:

Active enhancers in mammals produce enhancer RNAs (eRNAs) that are bidirectionally transcribed, unspliced, and unstable. Enhancer regions are also enriched with long noncoding RNA (lncRNA) transcripts, which are typically spliced and substantially more stable. In order to explore the relationship between these two classes of RNAs, we analyzed DNase hypersensitive sites with evidence of bidirectional transcription, which we termed eRNA-producing centers (EPCs). EPCs found very close to transcription start sites of lncRNAs exhibit attributes of both enhancers and promoters, including distinctive DNA motifs and a characteristic chromatin landscape. These EPCs are associated with higher enhancer activity, driven at least in part by the presence of conserved, directional splicing signals that promote lncRNA production, pointing at a causal role of lncRNA processing in enhancer activity. Together, our results suggest that the conserved ability of some enhancers to produce lncRNAs augments their activity in a manner likely mediated through lncRNA maturation.
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http://dx.doi.org/10.1016/j.cels.2018.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542670PMC
November 2018

A conserved abundant cytoplasmic long noncoding RNA modulates repression by Pumilio proteins in human cells.

Nat Commun 2016 07 13;7:12209. Epub 2016 Jul 13.

Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.

Thousands of long noncoding RNA (lncRNA) genes are encoded in the human genome, and hundreds of them are evolutionarily conserved, but their functions and modes of action remain largely obscure. Particularly enigmatic lncRNAs are those that are exported to the cytoplasm, including NORAD-an abundant and highly conserved cytoplasmic lncRNA. Here we show that most of the sequence of NORAD is comprised of repetitive units that together contain at least 17 functional binding sites for the two mammalian Pumilio homologues. Through binding to PUM1 and PUM2, NORAD modulates the mRNA levels of their targets, which are enriched for genes involved in chromosome segregation during cell division. Our results suggest that some cytoplasmic lncRNAs function by modulating the activities of RNA-binding proteins, an activity which positions them at key junctions of cellular signalling pathways.
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http://dx.doi.org/10.1038/ncomms12209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947167PMC
July 2016

Optical, electrical and surface plasmon resonance methods for detecting telomerase activity.

Anal Chem 2010 Oct;82(20):8390-7

Three different sensing platforms for the analysis of telomerase activity in human cells are described. One sensing platform involves the label-free analysis of the telomerase activity by a field-effect-transistor (FET) device. The telomerase-induced extension of a primer associated with the gate of the FET device, in the presence of the nucleotide mixture dNTPs, alters the gate potential, and this allows the detection of telomerase extracted from 65 ± 10 293T (transformed human embryonic kidney) cells/μL. The second sensing platform involves the optical detection of telomerase using CdSe/ZnS quantum dots (QDs). The telomerase-stimulated telomerization of the primer-functionalized QDs in the presence of the nucleotide mixture dNTPs results in the synthesis of the G-rich telomeres. The stacking of hemin on the self-organized G-quadruplexes found on the telomers results in the electron transfer quenching of the QDs, thus providing an optical readout signal. This method enables the detection of telomerase originating from 270 ± 20 293T cells/μL. The third sensing method involves the amplified surface plasmon resonance (SPR) detection of telomerase activity. The telomerization of a primer associated with Au film-coated glass slides, in the presence of telomerase and the nucleotide mixture (dNTPs), results in the formation of telomeres on the surface, and these alter the dielectric properties of the surface resulting in a shift in the SPR spectrum. The hybridization of Au NPs functionalized with nucleic acids complementary to the telomere repeat units with the telomeres amplifies the SPR shifts due to the coupling between the local plasmon of the NPs and the surface plasmon wave. This method enables the detection of telomerase extracted from 18 ± 3 293T cells/μL.
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http://dx.doi.org/10.1021/ac101976tDOI Listing
October 2010