Post-Transcriptional Regulation Of Human Interleukin-3 Mrna By The Adenosine/Uridine Rich Element

Human interleukin‐3 (IL‐3) is a cytokine that stimulates the growth and differentiation of early lymphoid stem cells and has been implicated in cancer. IL‐3 is a member of a class of transiently expressed mRNAs that harbor Adenosine/Uridine‐Rich Elements (ARE) in their 3′‐UTRs (untranslated region). These AREs play a role in post‐transcriptional control by altering mRNA stability and/or translation. The regulatory effects of AREs are often mediated by specific ARE‐binding proteins (ARE‐BPs). To understand how the AREs and ARE‐BPs in the 3′‐UTR of the IL‐3 mRNA regulate its expression, we constructed a series of firefly luciferase reporter chimeras harboring specific regions of the IL‐3 3′‐UTR. Transient transfection and in‐vitro translation assays of the luciferase‐IL‐3 3′UTR reporter constructs showed a significant reduction in luciferase activity. In addition electrophoretic mobility shift assays demonstrated the formation of several protein complexes in the IL‐3 3′‐UTR regions. Together, these results provide evidence for ARE‐dependent post‐transcriptional control of the human IL‐3 mRNA. JAGF is supported by FIPI‐UPR. This work is supported by grants to C.I.G. (KO1 HL‐04355‐05, GM008102‐3052, U54 CA96297‐03, AABRE‐P20 RR‐016470 from NCRR, RISE 2R25GM61151, PR‐LSAMP).