text: The 3′-UTR of mRNA has a great variety of regulatory functions that are controlled by the physical characteristics of the region. One such characteristic is the length of the 3′-UTR, which in the mammalian genome has considerable variation. This region of the mRNA transcript can range from 60 nucleotides to about 4000. On average the length for the 3′-UTR in humans is approximately 800 nucleotides, while the average length of 5-UTRs is only about 200 nucleotides. The length of the 3′-UTR is significant since longer 3′-UTRs are associated with lower levels of gene expression. One possible explanation for this phenomenon is that longer regions have a higher probability of possessing more miRNA binding sites that have the ability to inhibit translation. In addition to length, the nucleotide composition also differs significantly between the 5 and 3′-UTR. The mean G+C percentage of the 5-UTR in warm-blooded vertebrates is about 60% as compared to only 45% for 3′-UTRs. This is important because an inverse correlation has been observed between the G+C% of 5 and 3′-UTRs and their corresponding lengths. The UTRs that are GC-poor tend to be longer than those located in GC-rich genomic regions.
  Sequences within the 3′-UTR also have the ability to degrade or stabilize the mRNA transcript. Modifications that control a transcripts stability allow expression of a gene to be rapidly controlled without altering translation rates. One group of elements in the 3′-UTR that can help destabilize an mRNA transcript are the AU-rich elements (AREs). These elements range in size from 50 to 150 base pairs and generally contain multiple copies of the pentanucleotide AUUUA. Early studies indicated that AREs can vary in sequence and fall into three main classes that differ in the number and arrangement of motifs. Another set of elements that is present in both the 5 and 3′-UTR are iron response elements (IREs). The IRE is a stem-loop structure within the untranslated regions of mRNAs that encode proteins involved in cellular iron metabolism. The mRNA transcript containing this element is either degraded or stabilized depending upon the binding of specific proteins and the intracellular iron concentrations.
  The 3′-UTR also contains sequences that signal additions to be made, either to the transcript itself or to the product of translation. For example, there are two different polyadenylation signals present within the 3′-UTR that signal the addition of the poly(A) tail. These signals initiate the synthesis of the poly(A) tail at a defined length of about 250 base pairs. The primary signal used is the nuclear polyadenylation signal (PAS) with the sequence AAUAAA located toward the end of the 3′-UTR. However, during early development cytoplasmic polyadenylation can occur instead and regulate the translational activation of maternal mRNAs. The element that controls this process is called the CPE which is AU-rich and located in the 3′-UTR as well. The CPE generally has the structure UUUUUUAU and is usually within 100 base pairs of the nuclear PAS. Another specific addition signaled by the 3′-UTR is the incorporation of selenocysteine at UGA codons of mRNAs encoding selenoproteins. Normally the UGA codon encodes for a stop of translation, but in this case a conserved stem-loop structure called the selenocysteine insertion sequence (SECIS) causes for the insertion of selenocysteine instead.