%0 Journal Article
%T Sex lethal and upstream ORFs: a bait-and-trap system for ribosomes
%A Peng Yao
%A Paul L Fox
%J Genome Biology
%D 2011
%I BioMed Central
%R 10.1186/gb-2011-12-7-121
%X Upstream open reading frames (uORFs) in mRNAs are short sequences in the 5' untranslated region (UTR) characterized by a start codon, a short open reading frame (ORF) and a stop codon, all upstream of the major start codon that initiates translation of the principal gene product. (The term UTR is actually a misnomer, precisely because of the existence of uORFs, and is more accurately referred to as transcript leader region [1].) A ribosome encountering a uORF has several options, including scanning through the uORF until the major ORF is encountered, translating the uORF and then reinitiating translation of the major ORF, or translating the uORF and then stalling. The latter case can lead to decreased translation of the major ORF, or possibly shortened mRNA half-life by nonsense-mediated decay [1]. Thus, uORFs present diverse opportunities for regulation of gene expression. The likely importance of uORFs is suggested by their presence in about half of all annotated transcripts in both humans and mice [2]. Analysis of a group of uORF-containing mRNAs showed that uORFs reduce protein expression by 30 to 80%. uORF-altering mutations have been predicted or confirmed in more than a dozen human-disease-associated genes [2]. The molecular mechanisms underlying the effect of uORFs on translation are not well understood. There is overwhelming evidence for the importance of mRNA secondary structure in uORF-mediated regulation of translation [3,4]; however, a role for specific 5' UTR-binding proteins is less certain. In an elegant report in Cell, Matthias Hentze and colleagues [5] elucidate a uORF-dependent mechanism by which the Drosophila mRNA-binding protein Sex lethal (Sxl) inhibits translation of its target transcript, male-specific lethal (msl)-2.In Drosophila, dosage compensation equalizes the expression of X-linked genes in males and females. In male flies, the msl-2-containing dosage compensation complex is required for hypertranscription of the single X chromosome [6
%U http://genomebiology.com/2011/12/7/121