Gene expression is a complex process regulated at multiple levels in eukaryotic cells. Translation frequently represents a pivotal step in the control of gene expression. Among the stages of translation, initiation is particularly important, as it governs ribosome recruitment and the efficiency of protein synthesis. The 5' untranslated region (5' UTR) of mRNA plays a key role in this process, often exhibiting a complicated and structured landscape. Numerous eukaryotic mRNAs possess long 5' UTRs that contain diverse regulatory elements, including RNA secondary structures, specific nucleotide motifs, and chemical modifications. These structural features can independently modulate translation through their intrinsic properties or by serving as platforms for trans-acting factors such as RNA-binding proteins. The dynamic nature of 5' UTR elements allows cells to fine-tune translation in response to environmental and cellular signals. Understanding these mechanisms is not only fundamental to molecular biology but also holds significant biomedical potential. Insights into 5' UTR-mediated regulation could drive advancements in synthetic biology and mRNA-based targeted therapies. This review outlines the current knowledge of the structural elements of the 5' UTR, the interplay between them, and their combined functional impact on translation.
Keywords: 5? UTR; IRES; RNA G-quadruplexes; TOP; lncRNA; m6A; pseudoknots; riboswitches; stem-loops; translation; uORF.