Systemic impact of small regulatory RNAs

Genetics, cell biology and development

MicroRNAs ("miRNAs") are small post-transcriptional regulators. The function of these small RNAs in animals has been well characterized at a molecular level, but their role is less well known at the macroscopic scale: how could miRNAs have any biological function if they repress most of their targets less than 2-fold (while inter-individual gene expression fluctuation typically exceeds 2-fold, and is buffered by homeostatic mechanisms)?
According to the current dogma, each miRNA regulates tens or hundreds of targets, yet several observations suggest miRNAs have a much weaker impact on animal biology. Our recent work also suggests that both experimental and computational miRNA target identification methods are heavily contaminated with false positives: these false positives may be truly repressed by miRNAs at the molecular scale, but such a small repressive effect fails to translate into a macroscopic phenotype for most genes.
Our work thus suggests that the biological role of miRNAs has been largely over-estimated. We are currently exploring practical consequences of this new theoretical framework, measuring the contribution of individual miRNA/target interactions to global in vivo phenotypes.
More generally, we are proposing a new vision of gene regulation: a regulatory target is not simply a gene that is affected by a regulatory pathway; it is a gene that is affected enough by the pathway – the extent of a measured regulation needs to be confronted to the robustness of biological systems to fluctuations.
 

figure 3 fr
To contact us by email: each of our email addresses follows the format first_name.family_name[at]igh.cnrs.fr (without accents)
Isabelle BUSSEAU
Gestionnaire parc binoculaires et injection
Researcher

0434359936
Herve SEITZ
Researcher

0434359936
Elisabeth HOUBRON
IT

0434359936

Publications of the team

A rationalized definition of general tumor suppressor microRNAs excludes miR-34a

Sophie Mockly, Élisabeth Houbron, Hervé Seitz

more

Mechanistic analysis of the enhanced RNAi activity by 6-mCEPh-purine at the 5´ end of the siRNA guide strand

Vincent Brechin, Fumikazu Shinohara, Jun-Ichi Saito, Hervé Seitz, Yukihide Tomari

more

Re-assessment of the involvement of Snord115 in the serotonin 2C receptor pathway in a genetically relevant mouse model.

Hebras J, Marty V, Personnaz J, Mercier P, Krogh N, Nielsen H, Aguirrebengoa M, Seitz H, Pradere JP, Guiard BP, Cavaille J

SETX (senataxin), the helicase mutated in AOA2 and ALS4, functions in autophagy regulation

Patricia Richard, Shuang Feng, Yueh-Lin Tsai, Wencheng Li, Paola Rinchetti, Ubayed Muhith, Juan Irizarry-Cole, Katharine Stolz, Lionel A Sanz, Stella Hartono, Mainul Hoque, Saba Tadesse, Hervé Seitz, Francesco Lotti, Michio Hirano, Frédéric Chédin, Bin Tian, James L Manley

Prospects and challenges of multi-omics data integration in toxicology.

Canzler S, Schor J, Busch W, Schubert K, Rolle-Kampczyk UE, Seitz H, Kamp H, von Bergen M, Buesen R, Hackermüller J


+ Systemic impact of small regulatory RNAs

Prospects and challenges of multi-omics data integration in toxicology.

Canzler S, Schor J, Busch W, Schubert K, Rolle-Kampczyk UE, Seitz H, Kamp H, von Bergen M, Buesen R, Hackermüller J


+ Systemic impact of small regulatory RNAs

Inconsistencies and Limitations of Current MicroRNA Target Identification Methods.

Mockly S, Seitz H

Editorial: miRNA Regulatory Pathways in Metazoans. Advances From in vivo and ex vivo Studies.

Amar L, Seitz H

On the number of functional microRNA targets.

Seitz H

Functional lability of RNA-dependent RNA polymerases in animals.

Pinzón N, Bertrand S, Subirana L, Busseau I, Escrivá H, Seitz H

Amphioxus functional genomics and the origins of vertebrate gene regulation.

Marlétaz F, Firbas PN, Maeso I, Tena JJ, Bogdanovic O, Perry M, Wyatt CDR, de la Calle-Mustienes E, Bertrand S, Burguera D, Acemel RD, van Heeringen SJ, Naranjo S, Herrera-Ubeda C, Skvortsova K, Jimenez-Gancedo S, Aldea D, Marquez Y, Buono L, Kozmikova I, Permanyer J, Louis A, Albuixech-Crespo B, Le Petillon Y, Leon A, Subirana L, Balwierz PJ, Duckett PE, Farahani E, Aury JM, Mangenot S, Wincker P, Albalat R, Benito-Gutiérrez È, Cañestro C, Castro F, D'Aniello S, Ferrier DEK, Huang S, Laudet V, Marais GAB, Pontarotti P, Schubert M, Seitz H, Somorjai I, Takahashi T, Mirabeau O, Xu A, Yu JK, Carninci P, Martinez-Morales JR, Crollius HR, Kozmik Z, Weirauch MT, Garcia-Fernàndez J, Lister R, Lenhard B, Holland PWH, Escriva H, Gómez-Skarmeta JL, Irimia M

Applying 'omics technologies in chemicals risk assessment: Report of an ECETOC workshop.

Buesen R, Chorley BN, da Silva Lima B, Daston G, Deferme L, Ebbels T, Gant TW, Goetz A, Greally J, Gribaldo L, Hackermüller J, Hubesch B, Jennen D, Johnson K, Kanno J, Kauffmann HM, Laffont M, McMullen P, Meehan R, Pemberton M, Perdichizzi S, Piersma AH, Sauer UG, Schmidt K, Seitz H, Sumida K, Tollefsen KE, Tong W, Tralau T, van Ravenzwaay B, Weber RJM, Worth A, Yauk C, Poole A

microRNA target prediction programs predict many false positives

Pinzon, N., Li, B., Martinez, L., Sergeeva, A., Presumey, J., Apparailly, F., Seitz, H

Issues in current microRNA target identification methods

Seitz H

The gastrula transition reorganizes replication origin selection in Caenorhabditis elegans

Rodríguez-Martínez, M., Pinzón, N., Ghommidh, C., Beyne, E., Seitz, H., Cayrou, C., Méchali, M.


+ Replication and Genome Dynamics

Advancing the use of noncoding RNA in regulatory toxicology: Report of an ECETOC workshop

Aigner A, Buesen R, Gant T, Gooderham N, Greim H, Hackermüller J, Hubesch B, Laffont M, Marczylo E, Meister G, Petrick JS, Rasoulpour RJ, Sauer UG, Schmidt K, Seitz H, Slack F, Sukata T, van der Vies SM, Verhaert J, Witwer KW, Poole A

Argonaute proteins regulate HIV-1 multiply spliced RNA and viral production in a Dicer independent manner

Eckenfelder A, Ségéral E, Pinzón N, Ulveling D, Amadori C, Charpentier M, Nidelet S, Concordet JP, Zagury JF, Paillart JC, Berlioz-Torrent C, Seitz H, Emiliani S, Gallois-Montbrun S.

Coding and non-coding variants in the SHOX2 gene in patients with early-onset atrial fibrillation

Hoffmann S, Clauss S, Berger IM, Weiß B, Montalbano A, Röth R, Bucher M, Klier I, Wakili R, Seitz H, Schulze-Bahr E, Katus HA, Flachsbart F, Nebel A, Guenther SP, Bagaev E, Rottbauer W, Kääb S, Just S, Rappold GA.

microRNAs and the evolution of complex multicellularity: identification of a large, diverse complement of microRNAs in the brown alga Ectocarpus

Tarver JE, Cormier A, Pinzón N, Taylor RS, Carré W, Strittmatter M, Seitz H, Coelho SM, Cock JM

Silencing of X-Linked MicroRNAs by Meiotic Sex Chromosome Inactivation

Royo H, Seitz H, ElInati E, Peters AH, Stadler MB, Turner JM

Cnidarian microRNAs frequently regulate targets by cleavage

Moran, Y., Fredman, D., Praher, D., Li Z. L., Meng Wee,L., Rentzsch, F., Zamore,P.D., Technau, U., Seitz H.

Quantitative aspects of RNA silencing in metazoans

Sergeeva, A., Restrepo, N.P., and Seitz, H.

Recognition of the pre-miRNA structure by Drosophila Dicer-1

Tsutsumi A, Kawamata T, Izumi N, Seitz H, Tomari Y

A 5´-uridine amplifies miRNA/miRNA* asymmetry in Drosophila by promoting RNA-induced silencing complex formation

Seitz H, Tushir JS, Zamore PD

MARTINEZ Laura
MARTINEZ Laura
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LI Blaise
LI Blaise
Institut Pasteur
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GASPAROVA Iveta
GASPAROVA Iveta
Comenius Unversity, Bratislava, Slovakia
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MAZE Delphine
MAZE Delphine
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PINZON Natalia
PINZON Natalia
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SZABO Michael
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KONISHI Hideaki
KONISHI Hideaki
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GATO Alexandre
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MERMAT Yousra
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DEMONT Lara
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CHOUBANI Linda
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SERGEEVA Anna
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MARTIN Pierre
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BILLAULT-CHAUMARTIN Ingrid
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#}

Thèses

Topic : Reciprocal repressions between microRNA and messenger RNA
Sophie MOCKLY 01/10/2017 - 31/12/2021
Thesis supervisor : Hervé SEITZ

Publications during the thesis :

1. Mockly S. et Seitz H. Inconsistencies and limitations of current microRNA target identification methods (2019) Methods Mol Biol, 1970:291-314 (lien Pubmed : https://pubmed.ncbi.nlm.nih.gov/30963499/)

2. Mockly S., Houbron É et Seitz H. A rationalized definition of tumor suppressor microRNAs excludes miR-34a (soumis, manuscrit accessible à : https://www.biorxiv.org/content/10.1101/2021.02.11.430795v4)

Lab phd theses

InteRNAt summer school

2021 issue of the InteRNAt summer school (November 2–6, 2021, in Sète):

Website of the event : https://internat21.sciencesconf.org/.

2019 issue of the InteRNAt summer school (October 6–10, 2019, in Sète):

Website of the event : https://internat.sciencesconf.org.

Content of the introductory lectures given during the first half-day of the summer school (in French)(introduction on RNAi, on microRNAs, and on the biochemistry of the RISC complex; exercises): freely downloadable here.

Collaborators

Collaborator Aim of the collaboration Common publications
Dr. Yukihide TOMARI
(université de Tõkyõ)
Web site
Analysis of structural determinants of microRNA biogenesis Kawamata et al. (2009)
Pubmed

Tsutsumi et al. (2011)
Pubmed
Dr. Ulrich TECHNAU
(université de Vienne)
Web site
Functional analysis of small regulatory RNAs in Nematostella vectensis Moran et al. (2014)
Pubmed
Dr. Fabian RENTZSCH
(SARS Center)
Web site
Functional analysis of small regulatory RNAs in Nematostella vectensis Moran et al. (2014)
Pubmed
Prof. Phillip D. ZAMORE
(école de médecine de
l'université du Massachusetts)
Web site
Functional analysis of small regulatory RNAs in Nematostella vectensis Moran et al. (2014)
Pubmed
Dr. James TURNER
(Crick Institute, Londres)
Web site
Analysis of the expression of microRNAs subjected to an epigenetic control in mammals Royo et al. (2015)
Pubmed
Dr. Denis TAGU
(INRA Rennes)
Web site
Characterization of small regulatory RNAs in pea aphid  
Dr. Florence APPARAILLY
(IRMB, Montpellier)
Web site
Measurement of inter-individual fluctuation in gene expression in neutrophils Pinzón et al. (2017)
Pubmed
Dr. Marcel MÉCHALI
(IGH, Montpellier)
Web site
Identification of replication origins in early Nematode development and epigenetic characterization Rodríguez-Martínez et al. (2017)
Pubmed
Dr. Mark COCK
(UMR 8227, Roscoff)
Web site
MicroRNA identification in the brown alga Ectocarpus silicosus Tarver et al. (2015)
Pubmed
Prof. Gudrun RAPPOLD
(UniversitätKlinikum, Heidelberg)
Web site
Identification of a microRNA binding site specific to patients with atrial fibrillation Hoffmann et al. (2016)
Pubmed
Dr. Hector ESCRIVA
(Observatoire océanologique de Banyuls)
Web site
Characterization of small RNAs in the cephalochordate Branchiostoma lanceolatum

Marlétaz et al. (2018) Pubmed

Pinzón et al. (2019) Pubmed

Dr. Sarah GALLOIS-MONTBRUN
(Institut Cochin, Paris)
Web site
Identification of Ago binding sites in HIV-1 viral RNA Eckenfelder et al. (2017)
Pubmed
Dr. James Manley
(Columbia university, New York, États-Unis)
Web site
Characterization of molecular consequences of SETX repression in human cells Richard et al. (2020) Pubmed 
Dr. Jérôme Cavaillé (CBI, Toulouse)
Web site

Evaluation of molecular and physiological consequences of the deletion of the SNORD115 RNA

Hebras et al. (2020) Pubmed

Slides of seminars given in public lecture

Computer programs

 Dépôt GitHub

Manuscrit "Mockly et al., 2022"

Manuscrit “Pinzón et al., 2019”

Nom de fichier Taille
02_RdRP_phylogeny.md 1.49 KB
Cipres_DataMARSV1short3MBLG.zip 77.66 MB
RDRPMARSV1alignHMMALIGNShortV3TRIM.fasta 206.61 KB
RdRPMARSV1.fa 467.16 KB
STDERR 0 bytes
STDOUT 1.25 MB
_JOBINFO.TXT 347 bytes
_scheduler_stderr.txt 634 bytes
done.txt 49 bytes
infile.nex.bz2 80.16 KB
infile.nex.ckp.bz2 83.41 KB
infile.nex.ckp7E.bz2 83.35 KB
infile.nex.con.tre.bz2 36.9 KB
infile.nex.mcmc.bz2 10.85 KB
infile.nex.parts.bz2 11.96 KB
infile.nex.run1.p.bz2 113.92 KB
infile.nex.run1.t.bz2 33.64 MB
infile.nex.run2.p.bz2 113.8 KB
infile.nex.run2.t.bz2 33.34 MB
infile.nex.trprobs.bz2 625.68 KB
infile.nex.tstat.bz2 8 KB
infile.nex.vstat.bz2 30.3 KB
ns/page_white_text.png" />paramfile.txt 61 bytes
scheduler.conf 65 bytes
ns/page_white_text.png" />start.txt 40 bytes
ns/page_white_text.png" />stderr.txt 0 bytes
ns/page_white_text.png" />stdout.txt 1.25 MB
ns/page_white_text.png" />term.txt 318 bytes
Nom de fichier Taille
03_Small_RNA-Seq.md 29.47 KB
B_lanceolatum_genome_bowtie2_index.tar.bz2 776.93 MB
B_lanceolatum_transcriptome_bowtie2_index.tar.bz2 152.04 MB
Bl71nemr.fa.bz2 128.94 MB
Chef3.sh 2.67 KB
Chef4.sh 2.92 KB
Convincing_pre-miRNA_hairpins.fa 6.26 KB
Fuses_lines_clean.pl 514 bytes
Gel_purification_8h_embryos.pdf 9.57 MB
Gel_purification_15h_embryos.pdf 9.6 MB
Gel_purification_36h_embryos.pdf 11.19 MB
Gel_purification_60h_embryos.pdf 10.16 MB
Gel_purification_adult_females.pdf 9.09 MB
Gel_purification_adult_males.pdf 8.48 MB
Junction_and_exonic_reads_blat_output.dat 172.2 KB
Module_ORF_detector.pl 2.01 KB
Module_ORF_detector_lower_case.pl 2.04 KB
Module_TXT_to_FA.pl 513 bytes
Module_converts_fastq_to_fasta.pl 539 bytes
Module_excludes_hairpin-matching_reads.pl 1.42 KB
Module_extract_from_fasta.pl 572 bytes
Module_extract_from_fastq.pl 671 bytes
Module_extracts_fastq_read_identifiers.pl 349 bytes
Module_extracts_miRNA_hairpins.pl 1.35 KB
Module_extracts_read_sequences.pl 748 bytes
Module_logo_for_hairpin-matching.pl 1.89 KB
Module_selects_from_blat_results.pl 4.35 KB
Module_unification.pl 1.7 KB
Orthologs_to_known_hairpins.fa 3.29 MB
R_commands_convincing_ORF-matching_reads 1.89 KB
R_commands_genomic_non_ncRNA-matching_size_dist 1.36 KB
R_commands_hairpin-matching_size_dist 1.76 KB
R_commands_hairpin_read_profile 2.76 KB
R_commands_plot_miRNAs_in_dvpt 1.91 KB
R_commands_size_distribution_September2017 4.01 KB
R_commands_transcriptome_non_hairpin-matching_size_dist 1.87 KB
R_commands_worm_convincing_ORF-matching_size_dist 1.88 KB
R_commands_worm_extragenomic_extratranscriptomic_size_dist 1.33 KB
R_commands_worm_genomic_non_ncRNA-matching_size_dist 1.34 KB
R_commands_worm_hairpin-matching_size_dist 1.74 KB
R_commands_worm_transcriptome_non_hairpin-matching_size_dist 1.85 KB
R_commands_worm_transcriptomic_extragenomic_size_dist 1.77 KB
RdRP_template_loci.bed 168 bytes
Script_C_elegans.sh 6.69 KB
Script_convincing_transcriptome-matching_not_matching_ncRNA_or_hairpins.sh 315 bytes
Script_mapping_extragenomic_on_RdRP_template_loci.sh 713 bytes
Script_mapping_on_RdRP_template_loci.sh 1.03 KB
Script_miRNAs_in_development.sh 5.38 KB
Script_transcriptome-matching_not_matching_ncRNA_or_hairpins.sh 1.05 KB
Statistics.dat 1.08 KB
Top_antisense_junction_mapped_mRNAs.dat 0 bytes
Top_sense_junction_mapped_mRNAs.dat 314 bytes
Transcripts_with_convicing_ORFs_in_Bla_annot_final_refTranscripts.fa.bz2 10.25 MB
Trimmed_fastq.tar 2.44 GB
abundant_B_lanceolatum_ncRNAs.fa 521.74 KB
blanc_evm+_rn.fa.bz2 7.72 MB
blat_output.psl.bz2 657.3 MB
cel_abundant_ncRNAs.fa 129.46 KB
cel_hairpinMar18.fa 37.51 KB
hairpinMar18.fa 5.85 MB
ns/page_white_text.png" />md5sum_Seitz.txt 3.6 KB
miRNA_abundance_in_development.dat 7.08 KB
unified1.fa 1.1 MB

Manuscrit "Mockly et Seitz, 2019"

Manuscrit "Pinzón et al., 2017"

Scripts et données pour la préparation des 6 figures :

Conversion des fichiers FCS de cytométrie en fichiers texte

  • Script de conversion (usage : ./read_FCS.py input.fcs output.txt) : script python.

Activity reports and evaluation

Context :

CNRS researchers have to submit every year a yearly activity report, and every 5 years they have to submit a “phased activity report” which is more detailed (as well as a “mid-phase activity report” in the middle of that 5 year-period). Following the merge of regions Midi-Pyrénées and Languedoc-Roussillon, laboratories in Languedoc-Roussillon joined the phase of Midi-Pyrénées laboratories, thus delaying by one year the evaluation which was scheduled for 2019 (it will take place in 2020).

In addition, laboratories are evaluated every 5 to 6 years by an international committee, which is assembled by HCERES (formerly known as AERES), which will then issue an evaluation report (in English).

Activity reports and evaluation reports for our team:

2022 mid-phase activity report of Hervé Seitz (December 2019 – June 2022) (in French)

2020 evaluation report of our team by HCERES (in English)

2020 phased activitiy report of Hervé Seitz (January 2014 – December 2019) (in French)

2016 mid-phase activity report of Hervé Seitz (January 2014 – September 2016) (in French)

2014 evaluation report of our team by AERES (in English)

2014 phased activity report of Hervé Seitz (January 2009 – December 2013) (in French)

Pour le grand public

« La technologie CRISPR/Cas9 » 
(compte-rendu de la conférence donnée par Hervé Seitz au colloque « Quelles limites pour les technosciences en santé ? » à Clermont-Ferrand le 13 mars 2018, et publié dans le n°15 de la Revue du Centre Michel de l'Hospital).

Parallèle entre l'informatique et la génétique
(édition du génome, débuggage, matérialité de l'information, ...) (interview donnée dans le cadre des Tic-Talks du LIG).

Les statistiques en science expérimentale. Principe, limitations, erreurs courantes, illustrées par les rumeurs pseudo-scientifiques sur la Covid-19
(visio-conférence donnée le 13 mars 2021 sur invitation du cercle zététique du Languedoc-Roussillon ; diaporama cliquable accessible ici).

Outreach videos :

Open questions

Molecular biology explained to your grandmother

Last results