Publications


MetamORF: A repository of unique short Open Reading Frames identified by both experimental and computational approaches for gene-level and meta-analysis (2021)

Choteau SA, Wagner A, Pierre P, Spinelli L, Brun C (2021). MetamORF: A repository of unique short Open Reading Frames identified by both experimental and computational approaches for gene-level and meta-analysis. Database. Under review.

Project at Theories and Approaches of Genomic Complexity, Turing Centre for Living Systems, Aix-Marseille Université and Centre d'Immunologie de Marseille Luminy, Turing Centre for Living Systems, Aix-Marseille Université

Abstract: The development of high-throughput technologies revealed the existence of non-canonical short open reading frames (sORFs) on most eukaryotic RNAs. They are ubiquitous genetic elements conserved across species and suspected to be involved in numerous cellular processes. MetamORF (https://metamorf.hb.univ-amu.fr/) aims to provide a repository of unique sORFs identified in the human and mouse genomes with both experimental and computational approaches. By gathering publicly available sORF data, normalizing them and summarizing redundant information, we were able to identify a total of 1,162,675 unique sORFs. Despite the usual characterization of ORFs as short, upstream or downstream, there is currently no clear consensus regarding the definition of these categories. Thus, the data has been reprocessed using a normalized nomenclature. MetamORF enables new analyses at loci, gene, transcript and ORF levels, that should offer the possibility to address new questions regarding sORF functions in the future. The repository is available through an user-friendly web interface, allowing easy browsing, visualization, filtering over multiple criteria and export possibilities. sORFs could be searched starting from a gene, a transcript, an ORF ID, looking in a genome area or browsing the whole repository for a species. The database content has also been made available through track hubs at UCSC Genome Browser. Finally, we demonstrated an enrichment of genes harboring upstream open reading frames (uORFs) among genes expressed in response to reticular stress.


Proteostasis in dendritic cells is controlled by the PERK signaling axis independently of ATF4 (2020)

Mendes A, Gigan JP, Rodriguez Rodrigues C, Choteau SA, Sanseau D, Barros D, Almeida C, Camosseto V, Chasson L, Paton AW, Paton JC, Argüello RJ, Lennon-Duménil A, Gatti E, Pierre P (2020). Proteostasis in dendritic cells is controlled by the PERK signaling axis independently of ATF4. Life Science Alliance. 21;4(2):e202000865 doi: 10.26508/lsa.202000865.

Project at Centre d'Immunologie de Marseille Luminy, Turing Centre for Living Systems, Aix-Marseille Université

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Abstract: In stressed cells, phosphorylation of eukaryotic initiation factor 2α (eIF2α) controls transcriptome-wide changes in mRNA translation and gene expression known as the integrated stress response. We show here that DCs are characterized by high eIF2α phosphorylation, mostly caused by the activation of the ER kinase PERK (EIF2AK3). Despite high p-eIF2α levels, DCs display active protein synthesis and no signs of a chronic integrated stress response. This biochemical specificity prevents translation arrest and expression of the transcription factor ATF4 during ER-stress induction by the subtilase cytotoxin (SubAB). PERK inactivation, increases globally protein synthesis levels and regulates IFN-β expression, while impairing LPS-stimulated DC migration. Although the loss of PERK activity does not impact DC development, the cross talk existing between actin cytoskeleton dynamics; PERK and eIF2α phosphorylation is likely important to adapt DC homeostasis to the variations imposed by the immune contexts.


Transcoronary gradients of HDL-associated microRNAs in unstable coronary artery disease (2018)

Choteau SA, Cuesta Torres LF, Barraclough JY, Elder AMM, Martínez GJ, Chen Fan WY, Shrestha S, Ong KL, Barter PJ, Celermajer DS, Rye KA, Patel S, Tabet F (2018). Transcoronary gradients of HDL-associated microRNAs in unstable coronary artery. International Journal of Cardiology. 253:138144 doi:10.1016/j.card.2017.09.190.

Project at Lipid Research Group, School of Medical Science, University of New South Wales

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Abstract: Aims: MicroRNAs (miRNAs) are transported on high-density lipoproteins (HDLs) and HDL-associated miRNAs are involved in intercellular communication. We explored HDL-associated miRNAs concentration gradients across the coronary circulation in stable and unstable coronary artery disease patients and whether changes in the transcoronary gradient were associated with changes in HDL composition and size.
Methods: Acute coronary syndrome (ACS, n = 17) patients, those with stable coronary artery disease (stable CAD, n = 19) and control subjects without CAD ( n = 6) were studied. HDLs were isolated from plasma obtained from the coronary sinus (CS), aortic root (arterial blood) and right atrium (venous blood). HDL-associated miRNAs (miR-16, miR-20a, miR-92a, miR-126, miR-222 and miR-223) were quantified by TaqMan miRNA assays. HDL particle sizes were determined by non-denaturing polyacrylamide gradient gel electrophoresis. HDL composition was measured immunoturbidometrically or enzymatically.
Results: A concentration gradient across the coronary circulation was observed for all the HDL-associated miRNAs. In ACS patients, there was a significant inverse transcoronary gradient for HDL-associated miR-16, miR-92a and miR-223 ( p < 0.05) compared to patients with stable CAD. Changes in HDL-miRNA transcoronary gradients were not associated with changes in HDL composition or size. Conclusion: HDLs are depleted of miR-16, miR-92a and miR-223 during the transcoronary passage in patients with ACS compared to patients with stable CAD.


High-Density Lipoprotein-associated miR-223 is altered after diet-induced weight loss in overweight and obese males (2016)

Tabet F, Cuesta Torres LF, Ong KL, Shrestha S, Choteau SA, Barter PJ, Clifton P, Rye KA (2016). High-Density Lipoprotein-associated miR-223 is altered after diet-induced weight loss in overweight and obese males. PLoS One. 11(3):e0151061 doi:10.1371/journal.pone.0151061.

Project at Lipid Research Group, School of Medical Science, University of New South Wales

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Abstract: Background and Aims: microRNAs (miRNAs) are small, endogenous non-coding RNAs that regulate metabolic processes, including obesity. The levels of circulating miRNAs are affected by metabolic changes in obesity, as well as in diet-induced weight loss. Circulating miRNAs are transported by high-density lipoproteins (HDL) but the regulation of HDL-associated miRNAs after diet-induced weight loss has not been studied. We aim to determine if HDL-associated miR-16, miR-17, miR-126, miR-222 and miR-223 levels are altered by diet-induced weight loss in overweight and obese males.
Methods: HDL were isolated from 47 subjects following 12 weeks weight loss comparing a high protein diet (HP, 30% of energy) with a normal protein diet (NP, 20% of energy). HDL-associated miRNAs (miR-16, miR-17, miR-126, miR-222 and miR-223) at baseline and after 12 weeks of weight loss were quantified by TaqMan miRNA assays. HDL particle sizes were determined by non-denaturing polyacrylamide gradient gel electrophoresis. Serum concentrations of human HDL constituents were measured immunoturbidometrically or enzymatically.
Results: miR-16, miR-17, miR-126, miR-222 and miR-223 were present on HDL from overweight and obese subjects at baseline and after 12 weeks of the HP and NP weight loss diets. The HP diet induced a significant decrease in HDL-associated miR-223 levels (p = 0.015), which positively correlated with changes in body weight (r = 0.488, p = 0.032). Changes in miR-223 levels were not associated to changes in HDL composition or size.
Conclusion: HDL-associated miR-223 levels are significantly decreased after HP diet-induced weight loss in overweight and obese males. This is the first study reporting changes in HDL-associated miRNA levels with diet-induced weight loss.