Translation of the human ABCE1 transcript is regulated by upstream open reading frames

Silva, Joana; Romão, Luísa

http://hdl.handle.net/10400.18/6742

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Authors

Silva, Joana

Romão, Luísa

Abstract(s)

Short upstream open reading frames (uORFs) are cis-acting elements located within the 5'-leader sequence of transcripts and are defined by an initiation codon in-frame with a termination codon located upstream or downstream of its main ORF (mORF) initiation codon. Recent genome-wide ribosome profiling (Ribo-seq) studies have confirmed the widespread presence of uORFs and have shown that many uORFs can initiate with non-AUG codons. uORFs can impact gene expression of the downstream mORF by triggering mRNA decay or by regulating translation. Based on 5’-leader sequence ribosome occupancy profiles from Ribo-seq analysis in HCT116 cells, we studied the role of 6 non-AUG and 5 AUG uORFs present in the human ABCE1 mRNA. Using a set of reporter genes expressed in HCT116 cells and luminometry assays, we have observed that there are three AUG uORFs acting in a fail-safe manner to inhibit translation from the main AUG, being this repression immune to eIF2 phosphorylation. Functional aspects and implications of this regulatory mechanism to cell physiology will be discussed.