Alternative translation initiation from two in-frame start codons in DHX33 gene

DHX33 has been shown to play key roles in promoting cell proliferation. We have previously found that DHX33 protein is a doublet. In this report, we discovered that DHX33 doublet is due to alternative translation initiation by two in-frame initiation codons. This is supported by studies from both cell lines and mouse models. DHX33 translation initiation from either AUG codon happens at equal efficiency. Short DHX33 protein has similar cellular location and functions with full-length DHX33. Our results suggest that leaky scanning normally occur in DHX33 mRNA translation, which may serve as a safeguard mechanism to ensure optimal DHX33 translation efficiency. This is the first report of DEAD/DEAH box proteins that can be regulated by alternative translation initiation.