User:DSKireai/sandbox

The five prime untranslated region (5' UTR) (also know 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 dependent on organism.

Length
The 5' UTR begins at the transcription start site and ends one nucleotide (nt) before the initiation codon (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 thousands 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.

Elements
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. Meanwhile 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), which have a great impact on the regulation of translation (see below).

Secondary Structure
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.

Prokaryotes
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 that such as the 50S ribosomal subunit that allows for translation to begin. Each of these steps regulates the initiation of translation.

Regulation of Operon Translation
In prokaryotes, most 5' UTRs form complex secondary structure that affects how the translational machinery can bind to it. One such example of this is the autoregulation of ribosomal proteins (r-proteins). It is known that r-proteins bind directly to the 5' UTR of

Preinitiation Complex Regulation
The regulation of translation in eukaryotes is more complex then 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.



Closed-loop Regulation
Another important regulator of translation is the interaction between 3' UTR and the 5' UTR. The closed-loop structure inhibits translation. This has been observed in Xenopus laevis in which eIF4E bound to the 5' cap interacts with Maskin bound to CPEB on the 3' UTR creating translationally inactive transcripts. This translational inhibition is lifted once CPEB is phosphorylated, displacing the Masking binding site, allowing for the polymerization of the PolyA tail, which can recruit the translational machinery by means of PABP. However, it is important to note that this mechanism has been under great scrutiny.

uORFs
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, occuring 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, know as an upstream AUG (uAUG). This codon can be scanned for by ribosomes and then translated to creates a product, which can regulate the translation of the main protein coding sequence or other uORFs that may exist on the same transcript.



Internal Ribosome Entry Sites and Viruses
Viruses (as well as some eukaryotic) 5' UTRs contain internal ribosome entry sites, which is a cap-independent method of translational activation. Instead of building up a complex at the 5' cap, the IRES allows for direct binding of the ribosomal complexes to the transcript to begin translation. The IRES enables the viral transcript to translate more efficiently due to the lack of needing a preinitation complex, allowing the virus to replicate quickly.

Peer Review
The article has a wealth of great information regarding not only the primary transcript, but other elements that it is involved with. However, much of the grammar needs to be tightened and polished. Also, some of the information presented is either misleading or bogged down in grammar. Also, there are many things which should be linked. Below are various edits which may be considered:


 * Introduction
 * Overall grammar check should be done.
 * "A primary transcript is the single-stranded RNA product synthesized by transcription of DNA, and processed in many ways to yield various functional RNAs such as mRNAs, tRNAs, and rRNAs to be used in translation" - your opening sentence is misleading. There are many primary transcripts, including rRNA and tRNA, that are never translated.
 * The sentence needs overall work. Consider breaking it into two sentences as the and is combining two unrelated thoughts.
 * You make want to consider merging precursor mRNA into your article.
 * You refer to the primary transcript being in the cell's nucleus. This is incorrect as bacteria also have primary transcript which undergo processing such as alternative splicing.
 * "Of all of these, alternative splicing is the factor that directly contributes to the diversity of mRNA found in cells" - I would consider removing this sentence. It is misleading.
 * Production of the Primary Transcript
 * Again, nucleus and translation usage must be watched.
 * There should be a link to the main transcription) page as most of this material is covered. i.e put Main Article : Transcription at the top of the section.
 * "RNA polymerase II of eukaryotes transcribes the primary transcript mRNA from the antisense DNA template in the 5' to 3' direction, and the newly synthesized mRNA is complimentary to this antisense strand of DNA (see Figure)." is extremely confusing. "primary transcript mRNA" has no meaning. I believe you are trying to say "transcribes a transcript destined to be processed into an mRNA''.
 * Regulation of primary transcript production
 * "Factors that lead to histone acetylation activate transcription while factors that lead to histone deacetylation inhibit transcription" is not necessarily true. Consider H3K4AC, which can repressive.
 * Primary transcript and RNA processing