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

Adv Biol Regul. 2023 Aug:89:100975. doi: 10.1016/j.jbior.2023.100975. Epub 2023 Jun 7.

Abstract

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.

Keywords: 5′ untranslated region; Eosinophils; Protein synthesis; S6 kinase; mRNA translation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions
  • Humans
  • Mutation
  • Protein Biosynthesis*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Ribosomal Protein S6 Kinases / genetics
  • Ribosomal Protein S6 Kinases / metabolism

Substances

  • RNA, Messenger
  • 5' Untranslated Regions
  • Ribosomal Protein S6 Kinases