Finding a needle in a haystack: looking for non-coding RNA functions

Dr. Martin Crespi, Université Paris-Saclay
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Dr. Martin Crespi

Abstract: The non-coding genome is the major part of the eukaryotic transcriptome and many long noncoding RNAs, or lncRNAs, were shown to act as positive or negative quantitative regulators of gene expression in last years. Multiple mechanisms involving chromatin, silencing, splicing, epigenetics, translation and the modulation of small si/miRNA action revealed new regulations that may be linked to evolutionary diversity of cell types and forms. In our laboratory, we have identified lncRNAs genome-wide acting through the regulation of chromatin conformation in space or by modulating alternative splicing (AS) of specific targets. The plant lncRNAs MARS or APOLO modify the epigenomic landscape of their target loci through the formation chromatin loops. In addition, we previously showed that the AS regulators NSRs (for Nuclear Speckle RNA-binding proteins) interact with the ALTERNATIVE SPLICING COMPETITOR or ASCO lncRNA. More recently, we showed that ASCO also binds to the highly conserved spliceosome components PRP8a and SMD1 hinting that ASCO can directly bind to the core of the spliceosome. Using a transient assay screen to search for AS modulation genome-wide, we could find 4 new lncRNAs affecting AS regulation. Hence, lncRNAs may integrate a dynamic network including conserved spliceosome proteins or epigenetic chromatin regulators to affect the transcriptional output of the transcriptome. LncRNAs may reveal novel mechanisms to modulate transcriptome reprogramming in eukaryotes.

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