5′‐ UTRs and Regulation

Abstract The 5′‐untranslated region (UTR) consists of the leading part of a cellular messenger ribonucleic acid (mRNA) from the 5′ end to the translation start codon AUG. Precursor mRNA is posttranscriptionally modified by the removal of introns and by the addition at the 5′ end of a 7‐methyl‐guanylate cap structure, which has a crucial role in translation initiation and regulating transcript stability. 5′‐UTRs and 3′‐UTRs are deeply involved in posttranscriptional regulation of gene expression through specific motifs or RNA base modifications that can affect mRNA stability, subcellular localisation, nuclear export, tissue specificity and efficiency of translation. 5‐UTR regulation of translation is modulated by several cis‐acting elements that may also interact with trans acting factors such as proteins or microRNAs. The best studied elements are secondary structures that affect ribosome scanning efficiency (i.e. iron‐responsive element), internal ribosome entry sites (IRESs) and upstream open reading frames (uORFs). Key Concepts 5′‐UTRs are involved in posttranscriptional regulation of gene expression. Elements located in 5′‐UTRs interfere with ribosome scanning and modulate translation of main AUG. Secondary structures can interfere with ribosome scanning and can be stabilised or destabilised by protein or RNA interaction. Upstream open reading frames (uORFs) may modulate translation efficiency regulating ribosome leaky scanning and translation reinitiation. Alternative spliced mRNAs or usage of alternative TSSs (transcription start sites) may produce transcripts with different 5′‐UTRs modulating translation efficiency.