An Upstream Open Reading Frame Regulates LST1 Expression during Monocyte Differentiation

The regulation of gene expression depends on the interplay of multiple factors at the transcriptional and translational level. Upstream open reading frames (uORFs) play an important role as translational repressors of main ORFs and their presence or usage in transcripts can be regulated by different mechanisms. The main objective of the present study was to assess whether uORFs regulate the expression of the MHC class III gene LST1. We report that expression of LST1 is tightly regulated by alternative transcription initiation and the presence of an uORF in the 5′-UTR of transcripts. Specifically, using EGFP reporter constructs in human HeLa and HEK-293T cells and flow cytometry as well as western blot analysis we found the uORF to reduce the expression of the main ORF by roughly two-thirds. Furthermore, we were able to correlate a previously detected increase in LST1 protein expression during monocyte differentiation with an increase of transcription initiation at an alternative exon that does not contain an uORF.