Targeting the Long Non-Coding RNA LINC00599-205 splicing by novel candidate drug ABX464 to produce the anti-inflammatory microRNA miR-124

Laurent Manchon (1) , Audrey Vautrin (2) , Aude Garcel (2) , Noëlie Campos (2) , Jamal Tazi (2)

1 IGMM - Institut de Génétique Moléculaire de Montpellier
2 Abivax

Many nascent long non-coding RNAs have received considerable attention in recent years because of their major regulatory roles in gene expression and signaling pathways at various levels. Indeed long non-coding RNAs undergo the same maturation steps as pre-mRNAs of protein-coding genes, but they are less efficiently spliced and polyadenylated in comparison to them. Here we focus on a specific human long non-coding RNA and we show the activity of a new candidate drug that potentially affect its splicing and generate an anti-HIV and anti-inflammatory effects driven by upregulation of microRNA biogenesis. To investigate this activity we combine the use of capture sequencing technology and an ab initio transcript assembly on cells from six healthy individuals. The sequencing depth of capture sequencing permitted us to assemble transcripts exhibiting a complex array of splicing patterns. In essence, we revealed that splicing of the long non-coding RNA is activated by the drug whereas this splicing was not present in untreated samples.

Mots clés: transcriptome assembly; splicing; anti-inflammatory; long non-coding RNAs; anti- HIV; microRNA; capture sequencing; regulatory

Domaines: Immunologie

Laurent Manchon, Audrey Vautrin, Aude Garcel, Noëlie Campos, Jamal Tazi. Targeting the Long Non-Coding RNA LINC00599-205 splicing by novel candidate drug ABX464 to produce the anti-inflammatory microRNA miR-124. American Journal of Biomedical Science & Research, 2020, 7 (2), pp.196-203. ⟨10.34297/AJBSR.2020.07.001140⟩. ⟨hal-02450788v2⟩