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A functional definition of "microRNA targets"

Hervé Seitz seminar

Published on 8 November 2021

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

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

Retransmission of the seminars (without the question part) available here:

Sophie Mockly (8 minutes):

Hervé Seitz:

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

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


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


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.

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