text: Another form of translational regulation in eukaryotes comes from unique elements on the 5′ UTR called upstream open reading frames (uORF). These elements are fairly common, occurring in 35–49% of all human genes. A uORF is a coding sequence located in the 5′ UTR located upstream of the coding sequences initiation site. These uORFs contain their own initiation codon, known as an upstream AUG (uAUG). This codon can be scanned for by ribosomes and then translated to create a product, which can regulate the translation of the main protein coding sequence or other uORFs that may exist on the same transcript.
  The translation of the protein within the main ORF after a uORF sequence has been translated is known as reinitiation. The process of reinitiation is known to reduce the translation of the ORF protein. Control of protein regulation is determined by the distance between the uORF and the first codon in the main ORF. A uORF has been found to increase reinitiation with the longer distance between its uAUG and the start codon of the main ORF, which indicates that the ribosome needs to reacquire translation factors before it can carry out translation of the main protein. For example, ATF4 regulation is performed by two uORFs further upstream, named uORF1 and uORF2, which contain three amino acids and fifty-nine amino acids, respectively. The location of uORF2 overlaps with the ATF4 ORF. During normal conditions, the uORF1 is translated, and then translation of uORF2 occurs only after eIF2-TC has been reacquired. Translation of the uORF2 requires that the ribosomes pass by the ATF4 ORF, whose start codon is located within uORF2. This leads to its repression. However, during stress conditions, the 40S ribosome will bypass uORF2 because of a decrease in concentration of eIF2-TC, which means the ribosome does not acquire one in time to translate uORF2. Instead, ATF4 is translated.