Regulation of alternative splicing of the nucleoredoxin-like 1
Dates:2 January 2018 - 29 June 2018
Date limite de candidature:29 June 2018
~ Jan-March 2018
~ April-June 2018
Rod-derived cone viability factor (RdCVF) is a truncatedthioredoxin protein of 109 residues, an alternative splice product ofthe nucleoredoxin-like 1 (NXNL1) gene secreted by rodphotoreceptors that prevents the loss of function and the death ofcone photoreceptors in the retina by stimulating aerobic glycolysis(Léveillard et al., Nature genetics 2004; Aït-Ali et al. Cell, 2015). Thesecond product of the NXNL1 gene, RdCVFL, is a 212 residuesthioredoxin expresses by both class of photoreceptors (Mei et al.,Antioxidants & redox signaling, 2016). It prevents damages triggeredby excess oxygen. The analysis of the human NXNL1 pre-mRNAsequence revealed a conserved RNA loop, immediatelydownstream of exon 1. This loop binds to two specific splicing factorsin vitro and is a candidate cis-acting element in intron retention.The student will participate in mini-gene reporter splicingassays of constructs delivered to the retina of the mouse usingrecombinant adeno-associated viral vectors to validate theimportance of this RNA loop for intron retention.Alternative splicing is at the evolutionary origin of the NXNL1gene as a super-thioredoxin system.
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