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.

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


Estelle Rebecq
Estelle REBECQ
PhD Student

Elisabeth HOUBRON


Publications of the team

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

Sophie Mockly, Élisabeth Houbron, Hervé Seitz


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


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

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

Issues in current microRNA target identification methods

Seitz H

microRNA target prediction programs predict many false positives

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

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.

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

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.

Silencing of X-Linked MicroRNAs by Meiotic Sex Chromosome Inactivation

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

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

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.

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

Seitz H, Tushir JS, Zamore PD

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

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

Thèses et hdr

Reciprocal regulation between microRNAs and their targets 08/12/2021

Defended by Sophie Mockly on 08/12/2021 under the supervision of Hervé Seitz

LI Blaise
LI Blaise
Institut Pasteur
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InteRNAt summer school

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

Website of the event :

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

Website of the event :

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.


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)

Tsutsumi et al. (2011)
Dr. Ulrich TECHNAU
(université de Vienne)
Web site
Functional analysis of small regulatory RNAs in Nematostella vectensis Moran et al. (2014)
(SARS Center)
Web site
Functional analysis of small regulatory RNAs in Nematostella vectensis Moran et al. (2014)
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)
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)
Dr. Denis TAGU
(INRA Rennes)
Web site
Characterization of small regulatory RNAs in pea aphid  
(IRMB, Montpellier)
Web site
Measurement of inter-individual fluctuation in gene expression in neutrophils Pinzón et al. (2017)
Dr. Marcel MÉCHALI
(IGH, Montpellier)
Web site
Identification of replication origins in early Nematode development and epigenetic characterization Rodríguez-Martínez et al. (2017)
Dr. Mark COCK
(UMR 8227, Roscoff)
Web site
MicroRNA identification in the brown alga Ectocarpus silicosus Tarver et al. (2015)
Prof. Gudrun RAPPOLD
(UniversitätKlinikum, Heidelberg)
Web site
Identification of a microRNA binding site specific to patients with atrial fibrillation Hoffmann et al. (2016)
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

(Institut Cochin, Paris)
Web site
Identification of Ago binding sites in HIV-1 viral RNA Eckenfelder et al. (2017)
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 and datasets

 GitHub repository

Mockly et al. (2022) Nucleic Acids Research 50(8):4703–4712 :

Scripts and datasets for the preparation of figures, supplementary figures and supplementary tables - 636Mo

Brechin et al. (2021) RNA 27(2):151-162 :

Scripts and intermediary data

Hebras et al. (2020) eLife 9:e60862 :

Scripts and intermediary data

Richard et al. (2020) Autophagy 17(8):1889–1906 : 

Scripts and intermediary data

Pinzón et al. (2019) PLoS Genetics 15(2):e1007915 : 

Mockly et Seitz (2019) Methods in Molecular Biology 1970:291–314 :

Scripts and datasets for the preparation of Table 1

Rodríguez-Martínez et al. (2017) Nature Structural and Molecular Biology 24(3):290–299 :

Scripts and intermediary data

Pinzón et al. (2017) Genome Research 27(2):234–245 :

Scripts and datasets for the preparation of all 6 figures :

Royo et al. (2015) PLoS Genetics 11(10):e1005461 :

Scripts and data for the generation of figures 2D, 3B and 4A

Conversion of cytometry FCS files into text files :

Conversion script (usage : ./ 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