A helicase links upstream ORFs and RNA structure

Abstract

Upstream open reading frames (uORFs) in 5' UTRs of eukaryotic mRNAs are increasingly recognized as important elements that regulate cellular protein synthesis. Since uORFs can start from non-AUG codons, an enormous number of potential uORF initiation sites exists in 5'UTRs. However, only a subset of these sites is used and it has been unclear how actual start sites are selected. Studies of the DEAD-box helicase Ded1p from S. cerevisiae show that translation of uORFs with non-AUG initiation codons occurs upstream of mRNA structures that emerge with defective Ded1p. The data designate mRNA structure as important determinant for non-AUG initiation sites of uORFs. Ded1p can control this RNA structure and thereby regulate uORF translation.

Keywords: CLIP; DEAD-box; Helicase; Meiosis; Near-cognate codon; RNA structure; Ribosome profiling; Riboswitch; Translation; Yeast; uORF.

Figure 1.. Defects in Ded1p cause translation initiation at near cognate codons that are proximal to mRNA structure.

Simplified schematics of the link between Ded1p function and activation of near cognate initiation condons in 5’UTRs.

Figure 2.. Remodeling of mRNA by Ded1p and activation of near cognate initiation codons.

Ded1p associates with the PIC at the mRNA entry site of the small ribosomal subunit (Helix 16). Rate constants in the scheme are provided for illustrative purposes, they were not measured.