[SocBiN] Virtual seminar on microRNA targets welcoming Herve Seitz

Thu Nov 4 14:06:19 CET 2021

Dear all,

In the framework of the small non-coding RNA bioinformatics club (https://smallrna-bioinformatics.eu/), we are happy to announce the virtual seminars of Sophie Mockly and Hervé Seitz about functional microRNA targets, and microRNA degradation.

The club will propose seminars every two months.

Start Monday November 8th at 4pm (CET, Berlin/Paris)

(3 pm London/Lisbon, 10am New-York, 7am San Francisco, 5pm Tel Aviv)

More information here: https://smallrna-bioinformatics.eu/Pages/Seminars/Seminar-Seitz.aspx

Tweet for easy re-transmission: https://twitter.com/Laurent_Guyon/status/1450381126032371713

Link to the Zoom conference: https://univ-grenoble-alpes-fr.zoom.us/j/96875973366?pwd=SlB3eGtaUVovK2dDeEpEWDROVVJsUT09

Alternate link if you don't plan to ask questions (comments are authorized in YouTube): https://www.youtube.com/watch?v=Vyz9Gp6C7FM

Main Speaker: Hervé Seitz, Research Director at CNRS, IGH, Montpellier, France

*Title: A functional definition of "microRNA targets": current issues, biological implications, perspectives for improvement*

Abstract:

MicroRNAs (miRNAs) guide repressive proteins onto specific target RNAs. Targets are recognized by sequence complementarity, and the biochemical rules for target recognition are well described, allowing precise computational predictions of molecular miRNA targets. Consequently, high-throughput molecular biology and computational predictions now largely agree on the lists of miRNA targets, and it may seem that the biological impact of miRNA-guided regulation could be faithfully predicted and modeled. Yet these results are contradicted by the observed in vivo phenotypes: while current molecular biology and bio-informatics identify hundreds of targets for each miRNA (suggesting that miRNAs control many biological processes), in vivo genetics shows that miRNA mutants tend to exhibit subtle, discrete phenotypes (usually specific to a given organ and a given biological pathway). We will discuss the reasons for such a discrepancy, their practical implications in terms of miRNA biology, and potential improvements in the functional assignment of miRNAs.

Short session speaker (8 minutes long): Sophie Mockly (PhD student)

*Title: Computational prediction of microRNA degradation inducers*

Abstract:

MicroRNAs constitute a large family of ~21-nt-long RNAs loaded by AGO proteins to form the miRISC complex, which silences specific target mRNAs. In metazoans, the miRISC complex binds to perfectly or imperfectly complementary sequences, present most commonly in the  3 ́ UTRs of target mRNAs, causing mRNA translational repression or deadenylation. The spatial and temporal distribution of microRNAs in organisms is tightly regulated, and aberrant microRNA expression leads to disease. Up to now, the regulation of microRNA levels has been mainly explained by the regulation of microRNA biogenesis alone, neglecting microRNA turnover pathways. However, recent studies have described an endogenous mechanism of microRNA degradation based on binding specific target RNAs to microRNAs with extensive complementarity. This emerging pathway, named TDMD for Target-Directed MicroRNA Degradation, enables highly specific microRNA decay subsequently to the proteolysis of AGO by the ubiquitin-proteasome pathway, and in this way, provides a new layer of microRNA regulation. To date, in vivo examples have been observed mainly in some viruses and only three TDMD events have been characterized in metazoans. Based on published data about target RNA patterns leading to TDMD and phylogenetic conservation, we developed a computational tool for the in silico identification of RNA sites that induce microRNA degradation through TDMD. Supplemented with published RNA-seq and small-RNA-seq data, our workflow allows focusing on cell-specific TDMD inducer candidates. Our search uncovered several convincing candidates in mouse neurons and their molecular characterization has been initiated.

References

• microRNA target prediction programs predict many false positives, by Natalia Pinzón, Blaise Li, Laura Martinez, Anna Sergeeva, Jessy Presumey, Florence Apparailly, and Hervé Seitz Genome Research, published on 2017 (https://genome.cshlp.org/content/27/2/234.full)

• On the Number of Functional microRNA Targets, by Hervé Seitz Molecular Biology and Evolution, published on 2019 (https://academic.oup.com/mbe/article/36/7/1596/5372676)

• A rationalized definition of tumor suppressor microRNAs excludes miR-34a, by Sophie Mockly, Élisabeth Houbron, and Hervé Seitz bioRxiv, pre-print published on 2021 (https://www.biorxiv.org/content/10.1101/2021.02.11.430795v4)

____________________________

Laurent GUYON, PhD – Bioinformatics
CEA IRIG (Interdisciplinary Research Institute of Grenoble<http://www.cea.fr/drf/IRIG/english/Pages/Presentation.aspx>)
BioHealth Department
BCI (Biology of Cancer and Infection laboratory<http://www.bci-lab.fr/en>)
UMR 1292 CEA/Inserm/Université Grenoble Alpes

CEA Grenoble - Bât C3 – Bureau 224
17 rue des Martyrs
38054 GRENOBLE Cedex 9

Tél : (+33)4.38.78.04.53
Fax : (+33)4 38 78 50 58
Email : laurent.guyon at cea.fr<mailto:laurent.guyon at cea.fr>
http://laurent.guyon.phd.free.fr/

Happy to share miRViz (free to use website to analyze your microRNA datasets): http://mirviz.prabi.fr/
Article: https://doi.org/10.1093/nar/gkaa259
Messages of the paper: https://twitter.com/Laurent_Guyon/status/1255487510563651586

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