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uORF Edit
An Upstream Open Reading Frame (uORF) is a very short Open Reading Frame (ORF) within the 5'UTR of a mRNA that mechanistically regulates translation.[1][2] Length of the uORF can vary among organism. They are fairly common, appearing in 35-49% of human genes. Expression of the uORF typically interferes with the expression of a downstream ORF, which can correspond to the gene under regulation. In bacteria, uORFs are called leader peptides, and were originally discovered on the basis of their impact on the regulation of genes involved in the synthesis or transport of amino acids.

RBP
RNA-binding proteins 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 from assembling.

Ferritin regulation
Iron levels in cells are maintained by translation regulation of many proteins involved in iron storage and metabolism. In low levels of iron, the ORF of the target mRNA is blocked by the binding of two iron-regulatory proteins (IRP1 and IRP2) to the iron-response element. When iron is high, then the two iron-regulatory proteins do not bind as strongly.

Reinitiation
Reinitiation refers to the ribosome's ability to translate separate ORFs within the same transcript. uORFs can control translation by their distance from the start codon. uORFs have been found to increase reinitiation with the increase in intercistronic distance, which indicate that the ribosome needs to reacquire translation factors before it can start translation of the start codon. 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.

Other Mechanisms
In addition to reinitiation, uORFs contribute to translation initiation based on:
 * The nucleotides of a uORF may code for a codon that leads to a highly structured mRNA, causing the ribosome to stall.
 * cis- and trans- regulation on translation of mORF.
 * Interactions with IRES sites.