Editing Messenger RNA (section)

=== Eukaryotic pre-mRNA processing ===
{{main|Post-transcriptional modification}}
[[File:Gene structure eukaryote 2 annotated.svg|thumb|DNA gene is transcribed to pre-mRNA, which is then processed to form a mature mRNA, and then lastly translated by a ribosome to a protein]]
Processing of mRNA differs greatly among [[eukaryote]]s, [[bacteria]], and [[archaea]]. Non-eukaryotic mRNA is, in essence, mature upon transcription and requires no processing, except in rare cases.<ref>{{Cite book| vauthors = Watson JD |author-link=James Watson |title=Molecular Biology of the Gene, 7th edition|publisher=Pearson Higher Ed USA|date=February 22, 2013|isbn=9780321851499}}</ref> Eukaryotic pre-mRNA, however, requires several processing steps before its transport to the cytoplasm and its translation by the ribosome.

==== Splicing ====
{{main|RNA splicing}}
The extensive processing of eukaryotic pre-mRNA that leads to the mature mRNA is the [[RNA splicing]], a mechanism by which [[intron]]s or [[outron]]s (non-coding regions) are removed and [[exon]]s (coding regions) are joined. <ref>{{cite journal | url=https://www.nature.com/articles/s41580-022-00545-z | doi=10.1038/s41580-022-00545-z | title=The physiology of alternative splicing | date=2023 | journal=Nature Reviews Molecular Cell Biology | volume=24 | issue=4 | pages=242–254 | pmid=36229538 | vauthors = Marasco LE, Kornblihtt AR }}</ref><ref>{{cite journal | url=https://www.nature.com/articles/s41576-022-00556-8 | doi=10.1038/s41576-022-00556-8 | title=Regulation of pre-mRNA splicing: Roles in physiology and disease, and therapeutic prospects | date=2023 | journal=Nature Reviews Genetics | volume=24 | issue=4 | pages=251–269 | pmid=36526860 | vauthors = Rogalska ME, Vivori C, Valcárcel J }}</ref>

==== 5' cap addition ====
{{main|5' cap}}
[[File:5' cap labeled.svg|thumb|5' cap structure]]
A ''5' cap'' (also termed an RNA cap, an RNA [[7-methylguanosine]] cap, or an RNA m<sup>7</sup>G cap) is a modified guanine nucleotide that has been added to the "front" or [[5' end]] of a eukaryotic messenger RNA shortly after the start of transcription. The 5' cap consists of a terminal 7-methylguanosine residue that is linked through a 5'-5'-triphosphate bond to the first transcribed nucleotide. Its presence is critical for recognition by the [[ribosome]] and protection from [[RNase]]s.{{cn|date=February 2024}}

Cap addition is coupled to transcription, and occurs co-transcriptionally, such that each influences the other. Shortly after the start of transcription, the 5' end of the mRNA being synthesized is bound by a [[Capping enzyme|cap-synthesizing complex]] associated with [[RNA polymerase]]. This [[enzyme|enzymatic]] complex [[catalyze]]s the chemical reactions that are required for mRNA capping. Synthesis proceeds as a multi-step [[biochemistry|biochemical]] reaction.{{cn|date=February 2024}}

====Editing====
In some instances, an mRNA will be [[RNA editing|edited]], changing the nucleotide composition of that mRNA. An example in humans is the [[apolipoprotein B#RNA editing|apolipoprotein B]] mRNA, which is edited in some tissues, but not others. The editing creates an early stop codon, which, upon translation, produces a shorter protein. Another well-defined example is A-to-I (adenosine to inosine) editing, which is carried out by double-strand specific adenosine-to inosine editing (ADAR) enzymes. This can occur in both the open reading frame and untranslated regions, altering the structural properties of the mRNA. Although essential for development, the exact role of this editing is not fully understood <ref>{{cite journal | doi=10.1186/gm508 | doi-access=free | title=Adenosine-to-inosine RNA editing and human disease | date=2013 | journal=Genome Medicine | volume=5 | issue=11 | page=105 | pmid=24289319 | pmc=3979043 | vauthors = Slotkin W, Nishikura K }}</ref>

==== Polyadenylation ====
{{main|Polyadenylation}}
[[File:Polyadenylation.png|thumb|Polyadenylation]]
Polyadenylation is the covalent linkage of a polyadenylyl moiety to a messenger RNA molecule. In eukaryotic organisms most messenger RNA (mRNA) molecules are polyadenylated at the 3' end, but recent studies have shown that short stretches of uridine (oligouridylation) are also common.<ref name="Choi_2012">{{cite journal | vauthors = Choi YS, Patena W, Leavitt AD, McManus MT | title = Widespread RNA 3'-end oligouridylation in mammals | journal = RNA | volume = 18 | issue = 3 | pages = 394–401 | date = March 2012 | pmid = 22291204 | pmc = 3285928 | doi = 10.1261/rna.029306.111 }}</ref> The [[messenger RNA#Poly(A) tail|poly(A) tail]] and the protein bound to it aid in protecting mRNA from degradation by exonucleases. Polyadenylation is also important for transcription termination, export of the mRNA from the nucleus, and translation. mRNA can also be polyadenylated in prokaryotic organisms, where poly(A) tails act to facilitate, rather than impede, exonucleolytic degradation.{{cn|date=February 2024}}

Polyadenylation occurs during and/or immediately after transcription of DNA into RNA. After transcription has been terminated, the mRNA chain is cleaved through the action of an endonuclease complex associated with RNA polymerase. After the mRNA has been cleaved, around 250 adenosine residues are added to the free 3' end at the cleavage site. This reaction is catalyzed by [[polyadenylate polymerase]]. Just as in [[alternative splicing]], there can be more than one polyadenylation variant of an mRNA.

Polyadenylation site mutations also occur. The primary RNA transcript of a gene is cleaved at the poly-A addition site, and 100–200 A's are added to the 3' end of the RNA. If this site is altered, an abnormally long and unstable mRNA construct will be formed.