A motif in the 5′untranslated region of messenger RNAs regulates protein synthesis in a S6 kinase-dependent manner

The 5′ untranslated regions (UTRs) in messenger RNAs (mRNAs) play an important role in the regulation of protein synthesis. We had previously identified a group of mRNAs that includes human semaphorin 7A (SEMA7A) whose translation is upregulated by the Erk/p90S6K pathway in human eosinophils, with a potential negative impact in asthma and airway inflammation. In the current study, we aimed to find a common 5′UTR regulatory cis-element, and determine its impact on protein synthesis. We identified a common and conserved 5′UTR motif GGCTG—[(C/G)T(C/G)]_n—GCC that was present in this group of mRNAs. Mutations of the first two GG bases in this motif in SEMA7A 5′UTR led to a complete loss of S6K activity dependence for maximal translation. In conclusion, the newly identified 5′UTR motif present in SEMA7A has a critical role in regulating S6K-dependent protein synthesis.