Editing Gene expression (section)

===mRNA processing===
{{main|Post-transcriptional modification}}

While transcription of prokaryotic protein-coding genes creates [[MRNA|messenger RNA]] (mRNA) that is ready for translation into protein, transcription of eukaryotic genes leaves a [[primary transcript]] of RNA (pre-RNA), which first has to undergo a series of modifications to become a mature RNA. Types and steps involved in the maturation processes vary between coding and non-coding preRNAs; ''i.e.'' even though preRNA molecules for both mRNA and [[Transfer RNA|tRNA]] undergo splicing, the steps and machinery involved are different.<ref>{{Cite book| vauthors = Krebs JE, Goldstein ES, Kilpatrick ST  |title=Lewin's genes XII |isbn=978-1-284-10449-3|location=Burlington, MA | publisher = Jones & Bartlett Learning |oclc=965781334|date=2017-03-02}}</ref> The processing of non-coding RNA is described below (non-coding RNA maturation).

The processing of pre-mRNA include 5′ ''capping'', which is set of enzymatic reactions that add [[7-methylguanosine]] (m<sup>7</sup>G) to the 5′ end of pre-mRNA and thus protect the RNA from degradation by [[exonucleases]].<ref>{{cite journal | vauthors = Ramanathan A, Robb GB, Chan SH | title = mRNA capping: biological functions and applications | journal = Nucleic Acids Research | volume = 44 | issue = 16 | pages = 7511–7526 | date = September 2016 | pmid = 27317694 | pmc = 5027499 | doi = 10.1093/nar/gkw551 }}</ref> The m<sup>7</sup>G cap is then bound by [[cap binding complex]] heterodimer (CBP20/CBP80), which aids in mRNA export to cytoplasm and also protect the RNA from [[Messenger RNA decapping|decapping]].<ref>{{cite journal | vauthors = Gonatopoulos-Pournatzis T, Cowling VH | title = Cap-binding complex (CBC) | journal = The Biochemical Journal | volume = 457 | issue = 2 | pages = 231–242 | date = January 2014 | pmid = 24354960 | pmc = 3901397 | doi = 10.1042/BJ20131214 }}</ref>

Another modification is 3′ ''cleavage and polyadenylation''.<ref>{{cite journal | vauthors = Neve J, Patel R, Wang Z, Louey A, Furger AM | title = Cleavage and polyadenylation: Ending the message expands gene regulation | journal = RNA Biology | volume = 14 | issue = 7 | pages = 865–890 | date = July 2017 | pmid = 28453393 | pmc = 5546720 | doi = 10.1080/15476286.2017.1306171 }}</ref> They occur if polyadenylation signal sequence (5′- AAUAAA-3′) is present in pre-mRNA, which is usually between protein-coding sequence and terminator.<ref>{{cite journal | vauthors = Borodulina OR, Kramerov DA | title = Transcripts synthesized by RNA polymerase III can be polyadenylated in an AAUAAA-dependent manner | journal = RNA | volume = 14 | issue = 9 | pages = 1865–1873 | date = September 2008 | pmid = 18658125 | pmc = 2525947 | doi = 10.1261/rna.1006608 }}</ref> The pre-mRNA is first cleaved and then a series of ~200 adenines (A) are added to form poly(A) tail, which protects the RNA from degradation.<ref>{{cite journal | vauthors = Munoz-Tello P, Rajappa L, Coquille S, Thore S | title = Polyuridylation in Eukaryotes: A 3'-End Modification Regulating RNA Life | journal = BioMed Research International | volume = 2015 | pages = 968127 | date = 2015 | pmid = 26078976 | pmc = 4442281 | doi = 10.1155/2015/968127 | doi-access = free }}</ref> The poly(A) tail is bound by multiple [[poly(A)-binding protein|poly(A)-binding proteins (PABPs)]] necessary for mRNA export and translation re-initiation.<ref>{{cite journal | vauthors = Passmore LA, Coller J | title = Roles of mRNA poly(A) tails in regulation of eukaryotic gene expression | journal = Nature Reviews. Molecular Cell Biology | volume = 23 | issue = 2 | pages = 93–106 | date = February 2022 | pmid = 34594027 | pmc = 7614307 | doi = 10.1038/s41580-021-00417-y }}</ref> In the inverse process of deadenylation, poly(A) tails are shortened by the [[CCR4-Not]] 3′-5′ exonuclease, which often leads to full transcript decay.<ref>{{cite journal | vauthors = Morozov IY, Jones MG, Razak AA, Rigden DJ, Caddick MX | title = CUCU modification of mRNA promotes decapping and transcript degradation in Aspergillus nidulans | journal = Molecular and Cellular Biology | volume = 30 | issue = 2 | pages = 460–469 | date = January 2010 | pmid = 19901075 | pmc = 2798463 | doi = 10.1128/MCB.00997-09 }}</ref>

[[Image:Pre-mRNA.svg|right|thumbnail|404x404px|alt=Pre-mRNA is spliced to form of mature mRNA.|Illustration of exons and introns in pre-mRNA and the formation of mature mRNA by splicing. The UTRs (in green) are non-coding parts of exons at the ends of the mRNA.]]
A very important modification of eukaryotic pre-mRNA is ''[[RNA splicing]]''. The majority of eukaryotic pre-mRNAs consist of alternating segments called [[exons]] and [[introns]].<ref>{{cite journal | vauthors = Darnell JE | title = Reflections on the history of pre-mRNA processing and highlights of current knowledge: a unified picture | journal = RNA | volume = 19 | issue = 4 | pages = 443–460 | date = April 2013 | pmid = 23440351 | pmc = 3677254 | doi = 10.1261/rna.038596.113 }}</ref> During the process of splicing, an RNA-protein catalytical complex known as [[spliceosome]] catalyzes two [[transesterification]] reactions, which remove an intron and release it in form of lariat structure, and then splice neighbouring exons together.<ref>{{cite journal | vauthors = Zhang L, Vielle A, Espinosa S, Zhao R | title = RNAs in the spliceosome: Insight from cryoEM structures | journal = Wiley Interdisciplinary Reviews. RNA | volume = 10 | issue = 3 | pages = e1523 | date = May 2019 | pmid = 30729694 | pmc = 6450755 | doi = 10.1002/wrna.1523 }}</ref> In certain cases, some introns or exons can be either removed or retained in mature mRNA.<ref>{{cite journal | vauthors = Hossain MA, Rodriguez CM, Johnson TL | title = Key features of the two-intron Saccharomyces cerevisiae gene SUS1 contribute to its alternative splicing | journal = Nucleic Acids Research | volume = 39 | issue = 19 | pages = 8612–8627 | date = October 2011 | pmid = 21749978 | pmc = 3201863 | doi = 10.1093/nar/gkr497 }}</ref> This so-called [[alternative splicing]] creates series of different transcripts originating from a single gene. Because these transcripts can be potentially translated into different proteins, splicing extends the complexity of eukaryotic gene expression and the size of a species [[proteome]].<ref>{{cite journal | vauthors = Baralle FE, Giudice J | title = Alternative splicing as a regulator of development and tissue identity | journal = Nature Reviews. Molecular Cell Biology | volume = 18 | issue = 7 | pages = 437–451 | date = July 2017 | pmid = 28488700 | pmc = 6839889 | doi = 10.1038/nrm.2017.27 }}</ref>

Extensive RNA processing may be an [[evolution|evolutionary advantage]] made possible by the nucleus of eukaryotes. In prokaryotes, transcription and translation happen together, whilst in eukaryotes, the [[nuclear membrane]] separates the two processes, giving time for RNA processing to occur.<ref>{{cite journal | vauthors = Baum B, Spang A | title = On the origin of the nucleus: a hypothesis | journal = Microbiology and Molecular Biology Reviews | volume = 87 | issue = 4 | pages = e0018621 | date = December 2023 | pmid = 38018971 | pmc = 10732040 | doi = 10.1128/mmbr.00186-21 }}</ref>