The 5’ flanking region is a region of DNA that is adjacent to the 5’ end of the gene. The 5’ flanking region contains the promoter, and may contain enhancers or other protein binding sites. It is the region of DNA that is not transcribed into RNA.
A messenger ribonucleic acid (mRNA) molecule codes for a protein through translation. The mRNA also contains regions that are not translated: in eukaryotes these include the 5’ untranslated region, 3’ untranslated region, 5’ cap and poly-A tail.
The five prime untranslated region (5’ UTR), can contain elements for controlling gene expression by way of regulatory elements. It begins at the transcription start site and ends one nucleotide (nt) before the start codon (usually AUG) of the coding region. In prokaryotes, the 5’ UTR usually contains a ribosome binding site (RBS), also known as the Shine Dalgarno sequence (AGGAGGU).
The 5’ UTR has a median length of ~150 nt in eukaryotes, but can be as long as several thousand bases. Some viruses and cellular genes have unusually long and structured 5’ UTRs which may impact gene expression. On average, 3’ UTR tend to be twice as long as the 5’ UTR. In prokaryotic mRNAs the 5’ UTR is normally shorter.
Several regulatory sequences may be found in the 5’ UTR:
Binding sites for proteins, that may affect the mRNA’s stability or translation, for example iron responsive elements, that regulate gene expression in response to iron.
Riboswitches.
Sequences that promote or inhibit translation initiation.
Introns within 5’ UTRs have been linked to regulation of gene expression and mRNA export.
Alternative splicing and variation of the transcription start site can produce alternative 5′UTRs. Diversity within the 5′UTR of a gene enables variation in expression, which is dependent on the regulatory elements contained in the alternative 5’ UTR. Mutations to sequences within the 5’ UTR as well as changes to the length of the 5’ UTR have been implicated in various human diseases, such as hereditary thrombocythaemia.
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