AUGs (uAUGs) and termination codons, which have a great impact on the regulation of translation (see below). Unlike prokaryotes, 5′ UTRs can harbor introns in eukaryotes. In humans, ~35% of all genes harbor introns within the 5′ UTR. Secondary structure As the 5′ UTR has high GC content, secondary structures often occur within it. Hairpin loops are one such secondary structure that can be located within the 5′ UTR. These secondary structures also impact the regulation of translation. Role in translational regulation Prokaryotes In bacteria, the initiation of translation occurs when IF-3, along with the 30S ribosomal subunit, bind to the Shine–Dalgarno (SD) sequence of the 5′ UTR. This then recruits many other proteins, such as the 50S ribosomal subunit, which allows for translation to begin. Each of these steps regulates the initiation of translation. Initiation in Archaea is less understood. SD sequences are much rarer, and the initiation factors have more in common with eukaryotic ones. There is no homolog of bacterial IF3. Some mRNAs are leaderless. In both domains, genes without Shine–Dalgarno sequences are also translated in a less understood manner. A requirement seems to be a lack of secondary structure near the initiation codon. Eukaryotes Pre-initiation complex regulation The regulation of translation in eukaryotes is more complex than in prokaryotes. Initially, the eIF4F complex is recruited to the 5′ cap, which in turn recruits the ribosomal complex to the 5′ UTR. Both eIF4E and eIF4G bind the 5′ UTR, which limits the rate at which translational initiation can occur. However, this is not the only regulatory step of translation that involves the 5′ UTR. RNA-binding proteins sometimes serve to prevent the pre-initiation complex from forming. An example is regulation of the msl2 gene. The protein SXL attaches to an intron segment located within the 5′ UTR segment of the primary transcript, which leads to the inclusion of the intron after processing. This sequence allows the recruitment of proteins that bind simultaneously to both the 5′ and 3′ UTR, not allowing translation proteins to assemble. However, it has also been noted that SXL can also repress translation of RNAs that do not contain a poly(A) tail, or more generally, 3′ UTR. Closed-loop regulation Another important regulator of translation is the interaction between 3′ UTR and the 5′ UTR. The closed-loop structure inhibits translation. This has been observed in Xenopus laevis, in which eIF4E bound to the 5′ cap