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Article ; Online: Establishing association between HLA-C*04:01 and severe COVID-19.

Warren, René L / Abraham, Rohan / Calingo, Marc / Garant, Jean-Michel / Jones, Steven J M / Birol, Inanc

2024 Volume 103, Issue 1, Page(s) e15355

MeSH term(s)	Humans ; COVID-19 ; HLA-C Antigens/genetics ; Alleles ; SARS-CoV-2 ; Gene Frequency
Chemical Substances	HLA-C Antigens
Language	English
Publishing date	2024-01-25
Publishing country	England
Document type	Letter
ZDB-ID	2845111-9
ISSN	2059-2310 ; 2059-2302
ISSN (online)	2059-2310
ISSN	2059-2302
DOI	10.1111/tan.15355
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Article ; Online: G4RNA screener web server: User focused interface for RNA G-quadruplex prediction.

Garant, Jean-Michel / Perreault, Jean-Pierre / Scott, Michelle S

Biochimie

2018 Volume 151, Page(s) 115–118

Abstract: Though RNA G-quadruplexes became a focus of study over a decade ago, the main challenge associated with the identification of new potential G-quadruplexes remains a bottleneck step. It slows the study of these non-canonical structures in nucleic acids, ... ...

Abstract	Though RNA G-quadruplexes became a focus of study over a decade ago, the main challenge associated with the identification of new potential G-quadruplexes remains a bottleneck step. It slows the study of these non-canonical structures in nucleic acids, and thus the understanding of their significance. The G4RNA screener is an accurate tool for the prediction of RNA G-quadruplexes but its deployment has brought to light an issue with its accessibility to G-quadruplex experts and biologists. G4RNA screener web server is a platform that provides a much needed interface to manage the input, parameters and result display of the main command-line ready tool. It is accessible at http://scottgroup.med.usherbrooke.ca/G4RNA_screener/.
MeSH term(s)	Computational Biology ; G-Quadruplexes ; Internet ; RNA/chemistry ; User-Computer Interface
Chemical Substances	RNA (63231-63-0)
Language	English
Publishing date	2018-06-06
Publishing country	France
Document type	Journal Article
ZDB-ID	120345-9
ISSN	1638-6183 ; 0300-9084
ISSN (online)	1638-6183
ISSN	0300-9084
DOI	10.1016/j.biochi.2018.06.002
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Article ; Online: Genome-wide detection of imprinted differentially methylated regions using nanopore sequencing.

Akbari, Vahid / Garant, Jean-Michel / O'Neill, Kieran / Pandoh, Pawan / Moore, Richard / Marra, Marco A / Hirst, Martin / Jones, Steven J M

eLife

2022 Volume 11

Abstract: Imprinting is a critical part of normal embryonic development in mammals, controlled by defined parent-of-origin (PofO) differentially methylated regions (DMRs) known as imprinting control regions. Direct nanopore sequencing of DNA provides a means to ... ...

Abstract	Imprinting is a critical part of normal embryonic development in mammals, controlled by defined parent-of-origin (PofO) differentially methylated regions (DMRs) known as imprinting control regions. Direct nanopore sequencing of DNA provides a means to detect allelic methylation and to overcome the drawbacks of methylation array and short-read technologies. Here, we used publicly available nanopore sequencing data for 12 standard B-lymphocyte cell lines to acquire the genome-wide mapping of imprinted intervals in humans. Using the sequencing data, we were able to phase 95% of the human methylome and detect 94% of the previously well-characterized, imprinted DMRs. In addition, we found 42 novel imprinted DMRs (16 germline and 26 somatic), which were confirmed using whole-genome bisulfite sequencing (WGBS) data. Analysis of WGBS data in mouse (
MeSH term(s)	Alleles ; Animals ; DNA Methylation ; Female ; Genomic Imprinting ; Germ Cells ; Mammals/genetics ; Mice ; Nanopore Sequencing ; Pregnancy
Language	English
Publishing date	2022-07-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.77898
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Article: Guanine Nucleotide-Binding Protein-Like 1 (GNL1) binds RNA G-quadruplex structures in genes associated with Parkinson’s disease

Turcotte, Marc-Antoine / Garant, Jean-Michel / Cossette-Roberge, Hélène / Perreault, Jean-Pierre

RNA biology. 2021 Sept. 02, v. 18, no. 9

2021

Abstract: RNAs are highly regulated at the post-transcriptional level in neurodegenerative diseases and just a few mutations can significantly affect the fate of neuronal cells. To date, the impact of G-quadruplex (G4) regulation in neurodegenerative diseases like ...

Abstract	RNAs are highly regulated at the post-transcriptional level in neurodegenerative diseases and just a few mutations can significantly affect the fate of neuronal cells. To date, the impact of G-quadruplex (G4) regulation in neurodegenerative diseases like Parkinson’s disease (PD) has not been analysed. In this study, in silico potential G4s located in deregulated genes related to the nervous system were initially identified and were found to be significantly enriched. Several G4 sequences found in the 5ʹ untranslated regions (5ʹUTR) of mRNAs associated with Parkinson’s disease were demonstrated to in fact fold in vitro by biochemical assays. Subcloning of the full-length 5ʹUTRs of these candidates upstream of a luciferase reporter system led to the demonstration that the G4s of both Parkin RBR E3 Ubiquitin Protein Ligase (PRKN) and Vacuolar Protein Sorting-Associated Protein 35 (VPS35) significantly repressed the translation of both genes in SH-SY5Y cells. Subsequently, a strategy of using label-free RNA affinity purification assays with either of these two G4 sequences as bait isolated the Guanine Nucleotide-Binding Protein-Like 1 (GNL1). The latter was shown to have a higher affinity for the G4 sequences than for their mutated version. This study sheds light on new RNA G-quadruplexes located in genes dysregulated in Parkinson disease and a new G4-binding protein, GNL1.
Keywords	Parkinson disease ; computer simulation ; guanine ; luciferase ; neurons ; nucleic acid conformation ; ubiquitin-protein ligase ; vacuoles
Language	English
Dates of publication	2021-0902
Size	p. 1339-1353.
Publishing place	Taylor & Francis
Document type	Article
ISSN	1555-8584
DOI	10.1080/15476286.2020.1847866
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Guanine Nucleotide-Binding Protein-Like 1 (GNL1) binds RNA G-quadruplex structures in genes associated with Parkinson's disease.

Turcotte, Marc-Antoine / Garant, Jean-Michel / Cossette-Roberge, Hélène / Perreault, Jean-Pierre

RNA biology

2020 Volume 18, Issue 9, Page(s) 1339–1353

Abstract	RNAs are highly regulated at the post-transcriptional level in neurodegenerative diseases and just a few mutations can significantly affect the fate of neuronal cells. To date, the impact of G-quadruplex (G4) regulation in neurodegenerative diseases like Parkinson's disease (PD) has not been analysed. In this study,
MeSH term(s)	5' Untranslated Regions ; G-Quadruplexes ; GTP-Binding Proteins/genetics ; GTP-Binding Proteins/metabolism ; Humans ; Mutation ; Neuroblastoma/genetics ; Neuroblastoma/metabolism ; Neuroblastoma/pathology ; Parkinson Disease ; Tumor Cells, Cultured ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism ; Vesicular Transport Proteins/genetics ; Vesicular Transport Proteins/metabolism
Chemical Substances	5' Untranslated Regions ; GNL1 protein, human ; VPS35 protein, human ; Vesicular Transport Proteins ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; parkin protein (EC 2.3.2.27) ; GTP-Binding Proteins (EC 3.6.1.-)
Language	English
Publishing date	2020-12-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1555-8584
ISSN (online)	1555-8584
DOI	10.1080/15476286.2020.1847866
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Article ; Online: Where are G-quadruplexes located in the human transcriptome?

Vannutelli, Anaïs / Belhamiti, Sarah / Garant, Jean-Michel / Ouangraoua, Aida / Perreault, Jean-Pierre

NAR genomics and bioinformatics

2020 Volume 2, Issue 2, Page(s) lqaa035

Abstract: It has been demonstrated that RNA G-quadruplexes (G4) are structural motifs present in transcriptomes and play important regulatory roles in several post-transcriptional mechanisms. However, the full picture of RNA G4 locations and the extent of their ... ...

Abstract	It has been demonstrated that RNA G-quadruplexes (G4) are structural motifs present in transcriptomes and play important regulatory roles in several post-transcriptional mechanisms. However, the full picture of RNA G4 locations and the extent of their implication remain elusive. Solely computational prediction analysis of the whole transcriptome may reveal all potential G4, since experimental identifications are always limited to specific conditions or specific cell lines. The present study reports the first in-depth computational prediction of potential G4 region across the complete human transcriptome. Although using a relatively stringent approach based on three prediction scores that accounts for the composition of G4 sequences, the composition of their neighboring sequences, and the various forms of G4, over 1.1 million of potential G4 (pG4) were predicted. The abundance of G4 was computationally confirmed in both 5' and 3'UTR as well as splicing junction of mRNA, appreciate for the first time in the long ncRNA, while almost absent of most of the small ncRNA families. The present results constitute an important step toward a full understanding of the roles of G4 in post-transcriptional mechanisms.
Language	English
Publishing date	2020-05-25
Publishing country	England
Document type	Journal Article
ISSN	2631-9268
ISSN (online)	2631-9268
DOI	10.1093/nargab/lqaa035
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Article ; Online: Motif independent identification of potential RNA G-quadruplexes by G4RNA screener.

Garant, Jean-Michel / Perreault, Jean-Pierre / Scott, Michelle S

Bioinformatics (Oxford, England)

2017 Volume 33, Issue 22, Page(s) 3532–3537

Abstract: ... at http://gitlabscottgroup.med.usherbrooke.ca/J-Michel/g4rna_screener.: Contact: jean-michel.garant ... usherbrooke.ca or jean-pierre.perreault@usherbrooke.ca or michelle.scott@usherbrooke.ca ...

Abstract	Motivation: G-quadruplex structures in RNA molecules are known to have regulatory impacts in cells but are difficult to locate in the genome. The minimal requirements for G-quadruplex folding in RNA (G≥3N1-7 G≥3N1-7 G≥3N1-7 G≥3) is being challenged by observations made on specific examples in recent years. The definition of potential G-quadruplex sequences has major repercussions on the observation of the structure since it introduces a bias. The canonical motif only describes a sub-population of the reported G-quadruplexes. To address these issues, we propose an RNA G-quadruplex prediction strategy that does not rely on a motif definition. Results: We trained an artificial neural network with sequences of experimentally validated G-quadruplexes from the G4RNA database encoded using an abstract definition of their sequence. This artificial neural network, G4NN, evaluates the similarity of a given sequence to known G-quadruplexes and reports it as a score. G4NN has a predictive power comparable to the reported G richness and G/C skewness evaluations that are the current state-of-the-art for the identification of potential RNA G-quadruplexes. We combined these approaches in the G4RNA screener, a program designed to manage and evaluate the sequences to identify potential G-quadruplexes. Availability and implementation: G4RNA screener is available for download at http://gitlabscottgroup.med.usherbrooke.ca/J-Michel/g4rna_screener. Contact: jean-michel.garant@usherbrooke.ca or jean-pierre.perreault@usherbrooke.ca or michelle.scott@usherbrooke.ca. Supplementary information: Supplementary data are available at Bioinformatics online.
MeSH term(s)	Databases, Nucleic Acid ; G-Quadruplexes ; Neural Networks, Computer ; Nucleotide Motifs ; RNA/chemistry ; Software
Chemical Substances	RNA (63231-63-0)
Language	English
Publishing date	2017-11-03
Publishing country	England
Document type	Journal Article
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btx498
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Article ; Online: Megabase-scale methylation phasing using nanopore long reads and NanoMethPhase.

Akbari, Vahid / Garant, Jean-Michel / O'Neill, Kieran / Pandoh, Pawan / Moore, Richard / Marra, Marco A / Hirst, Martin / Jones, Steven J M

Genome biology

2021 Volume 22, Issue 1, Page(s) 68

Abstract: The ability of nanopore sequencing to simultaneously detect modified nucleotides while producing long reads makes it ideal for detecting and phasing allele-specific methylation. However, there is currently no complete software for detecting SNPs, phasing ...

Abstract	The ability of nanopore sequencing to simultaneously detect modified nucleotides while producing long reads makes it ideal for detecting and phasing allele-specific methylation. However, there is currently no complete software for detecting SNPs, phasing haplotypes, and mapping methylation to these from nanopore sequence data. Here, we present NanoMethPhase, a software tool to phase 5-methylcytosine from nanopore sequencing. We also present SNVoter, which can post-process nanopore SNV calls to improve accuracy in low coverage regions. Together, these tools can accurately detect allele-specific methylation genome-wide using nanopore sequence data with low coverage of about ten-fold redundancy.
MeSH term(s)	Alleles ; Chromosomes, Human, X ; Computational Biology/methods ; DNA Methylation ; Epigenomics/methods ; Gene Frequency ; Genes, X-Linked ; Haplotypes ; Humans ; Mutation ; Nanopore Sequencing ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; Software ; X Chromosome Inactivation
Language	English
Publishing date	2021-02-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2040529-7
ISSN	1474-760X ; 1474-760X
ISSN (online)	1474-760X
ISSN	1474-760X
DOI	10.1186/s13059-021-02283-5
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Article ; Online: Motif-driven interactions between RNA and PRC2 are rheostats that regulate transcription elongation.

Rosenberg, Michael / Blum, Roy / Kesner, Barry / Aeby, Eric / Garant, Jean-Michel / Szanto, Attila / Lee, Jeannie T

Nature structural & molecular biology

2021 Volume 28, Issue 1, Page(s) 103–117

Abstract: Although polycomb repressive complex 2 (PRC2) is now recognized as an RNA-binding complex, the full range of binding motifs and why PRC2-RNA complexes often associate with active genes have not been elucidated. Here, we identify high-affinity RNA motifs ... ...

Abstract	Although polycomb repressive complex 2 (PRC2) is now recognized as an RNA-binding complex, the full range of binding motifs and why PRC2-RNA complexes often associate with active genes have not been elucidated. Here, we identify high-affinity RNA motifs whose mutations weaken PRC2 binding and attenuate its repressive function in mouse embryonic stem cells. Interactions occur at promoter-proximal regions and frequently coincide with pausing of RNA polymerase II (POL-II). Surprisingly, while PRC2-associated nascent transcripts are highly expressed, ablating PRC2 further upregulates expression via loss of pausing and enhanced transcription elongation. Thus, PRC2-nascent RNA complexes operate as rheostats to fine-tune transcription by regulating transitions between pausing and elongation, explaining why PRC2-RNA complexes frequently occur within active genes. Nascent RNA also targets PRC2 in cis and downregulates neighboring genes. We propose a unifying model in which RNA specifically recruits PRC2 to repress genes through POL-II pausing and, more classically, trimethylation of histone H3 at Lys27.
MeSH term(s)	Animals ; Cell Differentiation/genetics ; Cell Line ; Embryonic Stem Cells/metabolism ; Gene Expression Regulation/genetics ; Histones/metabolism ; Methylation ; Mice ; Nucleotide Motifs/genetics ; Polycomb Repressive Complex 2/metabolism ; Promoter Regions, Genetic/genetics ; Protein Biosynthesis/genetics ; Protein Biosynthesis/physiology ; RNA/genetics ; RNA/metabolism ; RNA Polymerase II/metabolism ; Transcription, Genetic/genetics ; Transcriptional Activation/genetics
Chemical Substances	Histones ; RNA (63231-63-0) ; Polycomb Repressive Complex 2 (EC 2.1.1.43) ; RNA Polymerase II (EC 2.7.7.-)
Language	English
Publishing date	2021-01-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2126708-X
ISSN	1545-9985 ; 1545-9993
ISSN (online)	1545-9985
ISSN	1545-9993
DOI	10.1038/s41594-020-00535-9
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Article: RNA G-Quadruplexes as Key Motifs of the Transcriptome.

Rouleau, Samuel / Jodoin, Rachel / Garant, Jean-Michel / Perreault, Jean-Pierre

Advances in biochemical engineering/biotechnology

2017 Volume 170, Page(s) 1–20

Abstract: G-Quadruplexes are non-canonical secondary structures that can be adopted under physiological conditions by guanine-rich DNA and RNA molecules. They have been reported to occur, and to perform multiple biological functions, in the genomes and ... ...

Abstract	G-Quadruplexes are non-canonical secondary structures that can be adopted under physiological conditions by guanine-rich DNA and RNA molecules. They have been reported to occur, and to perform multiple biological functions, in the genomes and transcriptomes of many species, including humans. This chapter focuses specifically on RNA G-quadruplexes and reviews the most recent discoveries in the field, as well as addresses the upcoming challenges researchers studying these structures face.
MeSH term(s)	Animals ; DNA/chemistry ; G-Quadruplexes ; Genome/genetics ; Humans ; RNA/chemistry ; Transcriptome/genetics
Chemical Substances	RNA (63231-63-0) ; DNA (9007-49-2)
Language	English
Publishing date	2017-03-31
Publishing country	Germany
Document type	Journal Article ; Review
ISSN	0724-6145
ISSN	0724-6145
DOI	10.1007/10_2017_8
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