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Five prime untranslated region

The 5′ untranslated region (5′ UTR) (also known as a leader sequence or leader RNA) is the region of an mRNA that is directly upstream from the initiation codon. This region is important for the regulation of translation of a transcript by differing mechanisms in viruses, prokaryotes and eukaryotes. While called untranslated, the 5′ UTR or a portion of it is sometimes translated into a protein product. This product can then regulate the translation of the main coding sequence of the mRNA. In many organisms, however, the 5′ UTR is completely untranslated, instead forming complex secondary structure to regulate translation. The 5′ UTR has been found to interact with proteins relating to metabolism; and proteins translate sequences within the 5′ UTR. In addition, this region has been involved in transcription regulation, such as the sex-lethal gene in Drosophila. Regulatory elements within 5′ UTRs have also been linked to mRNA export. The 5′ untranslated region (5′ UTR) (also known as a leader sequence or leader RNA) is the region of an mRNA that is directly upstream from the initiation codon. This region is important for the regulation of translation of a transcript by differing mechanisms in viruses, prokaryotes and eukaryotes. While called untranslated, the 5′ UTR or a portion of it is sometimes translated into a protein product. This product can then regulate the translation of the main coding sequence of the mRNA. In many organisms, however, the 5′ UTR is completely untranslated, instead forming complex secondary structure to regulate translation. The 5′ UTR has been found to interact with proteins relating to metabolism; and proteins translate sequences within the 5′ UTR. In addition, this region has been involved in transcription regulation, such as the sex-lethal gene in Drosophila. Regulatory elements within 5′ UTRs have also been linked to mRNA export. The 5′ UTR begins at the transcription start site and ends one nucleotide (nt) before the initiation sequence (usually AUG) of the coding region. In prokaryotes, the length of the 5′ UTR tends to be 3-10 nucleotides long, while in eukaryotes it tends to be anywhere from 100 to several thousand nucleotides long. For example, the ste11 transcript in Schizosaccharomyces pombe has a 2273 nucleotide 5′ UTR while the lac operon in Escherichia coli only has 7 nucleotides in its 5′ UTR. The differing sizes are likely due to the complexity of the eukaryotic regulation which the 5′ UTR holds, as well as the larger preinitiation complex which must form to begin translation. The elements of a eukaryotic and prokaryotic 5′ UTR differ greatly. The prokaryotic 5′ UTR contains a ribosome binding site (RBS), also known as the Shine Dalgarno sequence (AGGAGGU), which is usually 3-10 base pairs upstream from the initiation codon. In contrast, the eukaryotic 5′ UTR contains the Kozak consensus sequence (ACCAUGG), which contains the initiation codon. The eukaryotic 5′ UTR also contains cis-acting regulatory elements called upstream open reading frames (uORFs) and upstream 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. As the 5′ UTR has a 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. In prokaryotes, the initiation of translation occurs when IF-3, along with the 30S ribosomal subunit, bind to the Shine-Dalgarno 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. 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 limit 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. Another important regulator of translation is the interaction between 3′ UTR and the 5′ UTR.

[ "Untranslated region", "Translation (biology)" ]
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