mRNA Structure Regulates Translation at Every Step

Abstract Precise, context-sensitive control of protein synthesis is critical in eukaryotic cells, and mRNA structure has emerged as a central mechanism for achieving this control. mRNA structures influence every stage of translation. During initiation, structures within 5′ untranslated regions modulate ribosome association with mRNA and the balance between translation of the main open reading frame and use of upstream or alternative start sites. During elongation, structures in the coding sequence govern ribosome pausing in ways that can either protect mRNA stability or trigger decay. During termination, structures downstream of primary stop codons promote readthrough to generate protein isoforms in a tissue-specific manner. mRNA structures are remodeled by helicase expression, post-transcriptional modifications, and translational programming to provide additional layers of regulation. We review recent advances illuminating diverse mechanisms by which RNA structure modulates translation.