Sébastien Pfeffer, PhD. Group leader at UPR 9002 – ARN CNRS
Contact
Sébastien Pfeffer
Phone
E-Mail
Website
UPR 9002 – ARN CNRS
Institut de Biologie Moléculaire et Cellulaire du CNRS
2 allée Konrad Roentgen
67084 Strasbourg Cedex
France
Research topics
- Determination of small RNA profiles in virus-infected cells
- Regulation of small RNAs biogenesis and stability
- Identification of target of viral small RNAs
- Perturbation of the RNA silencing machinery by viruses
Role in NetRNA
The group of Sébastien Pfeffer will contribute expertise in virology and small RNA profiling. The group will analyze the impact of virus infection on microRNAs and other small RNAs expression in cultured cells, mice and patient samples. The precise role played by RNA silencing during viral infection in mammals will be defined and the mechanisms by which microRNAs themselves are regulated will be deciphered.
Working Group
Publications
2024
Baldaccini, Morgane; Gaucherand, Léa; Chane-Woon-Ming, Béatrice; Messmer, Mélanie; Gucciardi, Floriane; Pfeffer, Sébastien
The helicase domain of human Dicer prevents RNAi-independent activation of antiviral and inflammatory pathways Article de journal
Dans: EMBO J, 2024, ISSN: 1460-2075.
@article{pmid38287188,
title = {The helicase domain of human Dicer prevents RNAi-independent activation of antiviral and inflammatory pathways},
author = {Morgane Baldaccini and Léa Gaucherand and Béatrice Chane-Woon-Ming and Mélanie Messmer and Floriane Gucciardi and Sébastien Pfeffer},
doi = {10.1038/s44318-024-00035-2},
issn = {1460-2075},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {EMBO J},
abstract = {In mammalian somatic cells, the relative contribution of RNAi and the type I interferon response during viral infection is unclear. The apparent inefficiency of antiviral RNAi might be due to self-limiting properties and mitigating co-factors of the key enzyme Dicer. In particular, the helicase domain of human Dicer appears to be an important restriction factor of its activity. Here, we study the involvement of several helicase-truncated mutants of human Dicer in the antiviral response. All deletion mutants display a PKR-dependent antiviral phenotype against certain viruses, and one of them, Dicer N1, acts in a completely RNAi-independent manner. Transcriptomic analyses show that many genes from the interferon and inflammatory response pathways are upregulated in Dicer N1 expressing cells. We show that some of these genes are controlled by NF-kB and that blocking this pathway abrogates the antiviral phenotype of Dicer N1. Our findings highlight the crosstalk between Dicer, PKR, and the NF-kB pathway, and suggest that human Dicer may have repurposed its helicase domain to prevent basal activation of antiviral and inflammatory pathways.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2023
Girardi, Erika; Messmer, Mélanie; Lopez, Paula; Fender, Aurélie; Chicher, Johana; Chane-Woon-Ming, Béatrice; Hammann, Philippe; Pfeffer, Sébastien
Proteomics-based determination of double-stranded RNA interactome reveals known and new factors involved in Sindbis virus infection Article de journal
Dans: RNA, vol. 29, no. 3, p. 361–375, 2023, ISSN: 1469-9001.
@article{pmid36617674b,
title = {Proteomics-based determination of double-stranded RNA interactome reveals known and new factors involved in Sindbis virus infection},
author = {Erika Girardi and Mélanie Messmer and Paula Lopez and Aurélie Fender and Johana Chicher and Béatrice Chane-Woon-Ming and Philippe Hammann and Sébastien Pfeffer},
doi = {10.1261/rna.079270.122},
issn = {1469-9001},
year = {2023},
date = {2023-03-01},
urldate = {2023-03-01},
journal = {RNA},
volume = {29},
number = {3},
pages = {361--375},
abstract = {Viruses are obligate intracellular parasites, which depend on the host cellular machineries to replicate their genome and complete their infectious cycle. Long double-stranded (ds)RNA is a common viral by-product originating during RNA virus replication and is universally sensed as a danger signal to trigger the antiviral response. As a result, viruses hide dsRNA intermediates into viral replication factories and have evolved strategies to hijack cellular proteins for their benefit. The characterization of the host factors associated with viral dsRNA and involved in viral replication remains a major challenge to develop new antiviral drugs against RNA viruses. Here, we performed anti-dsRNA immunoprecipitation followed by mass spectrometry analysis to fully characterize the dsRNA interactome in Sindbis virus (SINV) infected human cells. Among the identified proteins, we characterized SFPQ (splicing factor, proline-glutamine rich) as a new dsRNA-associated proviral factor upon SINV infection. We showed that SFPQ depletion reduces SINV infection in human HCT116 and SK-N-BE(2) cells, suggesting that SFPQ enhances viral production. We demonstrated that the cytoplasmic fraction of SFPQ partially colocalizes with dsRNA upon SINV infection. In agreement, we proved by RNA-IP that SFPQ can bind dsRNA and viral RNA. Furthermore, we showed that overexpression of a wild-type, but not an RNA binding mutant SFPQ, increased viral infection, suggesting that RNA binding is essential for its positive effect on the virus. Overall, this study provides the community with a compendium of dsRNA-associated factors during viral infection and identifies SFPQ as a new proviral dsRNA binding protein.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Lee, Seungjae; Jee, David; Srivastava, Sid; Yang, Acong; Ramidi, Abhinav; Shang, Renfu; Bortolamiol-Becet, Diane; Pfeffer, Sébastien; Gu, Shuo; Wen, Jiayu; Lai, Eric C
Promiscuous splicing-derived hairpins are dominant substrates of tailing-mediated defense of miRNA biogenesis in mammals Article de journal
Dans: Cell Rep, vol. 42, no. 2, p. 112111, 2023, ISSN: 2211-1247.
@article{pmid36800291,
title = {Promiscuous splicing-derived hairpins are dominant substrates of tailing-mediated defense of miRNA biogenesis in mammals},
author = {Seungjae Lee and David Jee and Sid Srivastava and Acong Yang and Abhinav Ramidi and Renfu Shang and Diane Bortolamiol-Becet and Sébastien Pfeffer and Shuo Gu and Jiayu Wen and Eric C Lai},
doi = {10.1016/j.celrep.2023.112111},
issn = {2211-1247},
year = {2023},
date = {2023-02-01},
urldate = {2023-02-01},
journal = {Cell Rep},
volume = {42},
number = {2},
pages = {112111},
abstract = {Canonical microRNA (miRNA) hairpins are processed by the RNase III enzymes Drosha and Dicer into ∼22 nt RNAs loaded into an Argonaute (Ago) effector. In addition, splicing generates numerous intronic hairpins that bypass Drosha (mirtrons) to yield mature miRNAs. Here, we identify hundreds of previously unannotated, splicing-derived hairpins in intermediate-length (∼50-100 nt) but not small (20-30 nt) RNA data. Since we originally defined mirtrons from small RNA duplexes, we term this larger set as structured splicing-derived RNAs (ssdRNAs). These associate with Dicer and/or Ago complexes, but generally accumulate modestly and are poorly conserved. We propose they contaminate the canonical miRNA pathway, which consequently requires defense against the siege of splicing-derived substrates. Accordingly, ssdRNAs/mirtrons comprise dominant hairpin substrates for 3' tailing by multiple terminal nucleotidyltransferases, notably TUT4/7 and TENT2. Overall, the rampant proliferation of young mammalian mirtrons/ssdRNAs, coupled with an inhibitory molecular defense, comprises a Red Queen's race of intragenomic conflict.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2022
Girardi, Erika; Messmer, Melanie; Lopez, Paula; Fender, Aurelie; Chicher, Johana; Chane-Woon-Ming, Beatrice; Hammann, Philippe; Pfeffer, Sebastien
Proteomics-based determination of double stranded RNA interactome reveals known and new factors involved in Sindbis virus infection Article de journal
Dans: RNA, 2022, ISSN: 1469-9001.
@article{pmid36617674,
title = {Proteomics-based determination of double stranded RNA interactome reveals known and new factors involved in Sindbis virus infection},
author = {Erika Girardi and Melanie Messmer and Paula Lopez and Aurelie Fender and Johana Chicher and Beatrice Chane-Woon-Ming and Philippe Hammann and Sebastien Pfeffer},
doi = {10.1261/rna.079270.122},
issn = {1469-9001},
year = {2022},
date = {2022-12-01},
urldate = {2022-12-01},
journal = {RNA},
abstract = {Viruses are obligate intracellular parasites, which depend on the host cellular machineries to replicate their genome and complete their infectious cycle. Long double stranded (ds)RNA is a common viral by-product originating during RNA virus replication and is universally sensed as a danger signal to trigger the antiviral response. As a result, viruses hide dsRNA intermediates into viral replication factories and have evolved strategies to hijack cellular proteins for their benefit. The characterization of the host factors associated with viral dsRNA and involved in viral replication remains a major challenge to develop new antiviral drugs against RNA viruses. Here, we performed anti-dsRNA immunoprecipitation followed by mass spectrometry analysis to fully characterize the dsRNA interactome in Sindbis virus (SINV) infected human cells. Among the identified proteins, we characterized SFPQ (Splicing factor, proline-glutamine rich) as a new dsRNA-associated proviral factor upon SINV infection. We showed that SFPQ depletion reduces SINV infection in human HCT116 and SK-N-BE(2) cells, suggesting that SFPQ enhances viral production. We demonstrated that the cytoplasmic fraction of SFPQ partially colocalizes with dsRNA upon SINV infection. In agreement, we proved by RNA-IP that SFPQ can bind dsRNA and viral RNA. Furthermore, we showed that overexpression of a wild type, but not an RNA binding mutant SFPQ, increased viral infection, suggesting that RNA binding is essential for its positive effect on the virus. Overall, this study provides the community with a compendium of dsRNA-associated factors during viral infection and identifies SFPQ as a new proviral dsRNA binding protein.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Vilimova, M.; Pfeffer, S.
Post-transcriptional regulation of polycistronic microRNAs Article de journal
Dans: Wiley Interdiscip Rev RNA, p. e1749, 2022, ISSN: 1757-7012.
@article{pmid35702737,
title = {Post-transcriptional regulation of polycistronic microRNAs},
author = {M. Vilimova and S. Pfeffer},
doi = {10.1002/wrna.1749},
issn = {1757-7012},
year = {2022},
date = {2022-06-01},
urldate = {2022-06-01},
journal = {Wiley Interdiscip Rev RNA},
pages = {e1749},
abstract = {An important proportion of microRNA (miRNA) genes tend to lie close to each other within animal genomes. Such genomic organization is generally referred to as miRNA clusters. Even though many miRNA clusters have been greatly studied, most attention has been usually focused on functional impacts of clustered miRNA co-expression. However, there is also another compelling aspect about these miRNA clusters, their polycistronic nature. Being transcribed on a single RNA precursor, polycistronic miRNAs benefit from common transcriptional regulation allowing their coordinated expression. And yet, numerous reports have revealed striking discrepancies in the accumulation of mature miRNAs produced from the same cluster. Indeed, the larger polycistronic transcripts can act as platforms providing unforeseen post-transcriptional regulatory mechanisms controlling individual miRNA processing, thus leading to differential miRNA expression, and sometimes even challenging the general assumption that polycistronic miRNAs are co-expressed. In this review, we aim to address the current knowledge about how miRNA polycistrons are post-transcriptionally regulated. In particular, we will focus on the mechanisms occurring at the level of the primary transcript, which are highly relevant for individual miRNA processing and as such have a direct repercussion on miRNA function within the cell. This article is categorized under: RNA Processing > Processing of Small RNAs Regulatory RNAs/RNAi/Riboswitches > Biogenesis of Effector Small RNAs RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}