Editing Gene expression (section)

==Mechanism==

===Transcription===
[[File:simple transcription elongation1.svg|thumb|400px|alt=RNA polymerase moving along a stretch of DNA, leaving behind newly synthetized strand of RNA.|The process of transcription is carried out by RNA polymerase (RNAP), which uses DNA (black) as a template and produces RNA (blue).]]
{{main|Transcription (biology)}}
The production of a RNA copy from a DNA strand is called [[Transcription (biology)|transcription]], and is performed by [[RNA polymerase]]s, which add one [[ribonucleotide]] at a time to a growing RNA strand as per the [[Complementarity (molecular biology)|complementarity]] law of the nucleotide bases. This RNA is [[Complementarity (molecular biology)|complementary]] to the template 3′ → 5′ DNA strand,<ref name="Brueckner2009">{{cite journal | vauthors = Brueckner F, Armache KJ, Cheung A, Damsma GE, Kettenberger H, Lehmann E, Sydow J, Cramer P | title = Structure-function studies of the RNA polymerase II elongation complex | journal = Acta Crystallographica. Section D, Biological Crystallography | volume = 65 | issue = Pt 2 | pages = 112–120 | date = February 2009 | pmid = 19171965 | pmc = 2631633 | doi = 10.1107/S0907444908039875 | bibcode = 2009AcCrD..65..112B }}</ref> with the exception that [[thymine]]s (T) are replaced with [[uracil]]s (U) in the RNA and possible errors.

[[Bacterial transcription|In bacteria, transcription]] is carried out by a single type of RNA polymerase, which needs to bind a DNA sequence called a [[Pribnow box]] with the help of the [[sigma factor]] protein (σ factor) to start transcription. In eukaryotes, transcription is performed in the nucleus by three types of RNA polymerases, each of which needs a special DNA sequence called the [[Promoter (biology)|promoter]] and a set of DNA-binding proteins—[[transcription factors]]—to initiate the process (see regulation of transcription below). [[RNA polymerase I]] is responsible for transcription of ribosomal RNA (rRNA) genes. [[RNA polymerase II]] (Pol II) transcribes all protein-coding genes but also some non-coding RNAs (''e.g.'', snRNAs, [[snoRNA]]s or [[long non-coding RNA]]s). [[RNA polymerase III]] transcribes [[5S rRNA]], transfer RNA (tRNA) genes, and some small non-coding RNAs (''e.g.'', [[7SK RNA|7SK]]). Transcription ends when the polymerase encounters a sequence called the [[Terminator (genetics)|terminator]].

===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>

===Non-coding RNA maturation===
{{main|TRNA#tRNA biogenesis|l1=tRNA maturation|RRNA#Prokaryotes vs. Eukaryotes|l2=rRNA maturation|MicroRNA#Biogenesis|l3=miRNA maturation}}
In most organisms [[ncRNA|non-coding genes (ncRNA)]] are transcribed as precursors that undergo further processing. In the case of ribosomal RNAs (rRNA), they are often transcribed as a pre-rRNA that contains one or more rRNAs. The pre-rRNA is cleaved and modified ([[2′-O-methylation|2′-''O''-methylation]] and [[pseudouridine]] formation) at specific sites by approximately 150 different small nucleolus-restricted RNA species, called snoRNAs. SnoRNAs associate with proteins, forming snoRNPs. While snoRNA part basepair with the target RNA and thus position the modification at a precise site, the protein part performs the catalytical reaction. In eukaryotes, in particular a snoRNP called RNase, MRP cleaves the [[45S pre-rRNA]] into the [[28S ribosomal RNA|28S]], [[5.8S ribosomal RNA|5.8S]], and [[18S rRNA]]s. The rRNA and RNA processing factors form large aggregates called the [[nucleolus]].<ref name="Sirri2008">{{cite journal | vauthors = Sirri V, Urcuqui-Inchima S, Roussel P, Hernandez-Verdun D | title = Nucleolus: the fascinating nuclear body | journal = Histochemistry and Cell Biology | volume = 129 | issue = 1 | pages = 13–31 | date = January 2008 | pmid = 18046571 | pmc = 2137947 | doi = 10.1007/s00418-007-0359-6 }}</ref>

In the case of transfer RNA (tRNA), for example, the 5′ sequence is removed by [[RNase P]],<ref name="pmid9759486">{{cite journal | vauthors = Frank DN, Pace NR | title = Ribonuclease P: unity and diversity in a tRNA processing ribozyme | journal = Annual Review of Biochemistry | volume = 67 | pages = 153–180 | year = 1998 | pmid = 9759486 | doi = 10.1146/annurev.biochem.67.1.153 | doi-access = free }}</ref> whereas the 3′ end is removed by the [[Ribonuclease Z|tRNase Z]] enzyme<ref name="pmid17305600">{{cite journal | vauthors = Ceballos M, Vioque A | title = tRNase Z | journal = Protein and Peptide Letters | volume = 14 | issue = 2 | pages = 137–145 | year = 2007 | pmid = 17305600 | doi = 10.2174/092986607779816050 }}</ref> and the non-templated 3′ CCA tail is added by a [[nucleotidyl transferase]].<ref name="pmid15498478">{{cite journal | vauthors = Weiner AM | title = tRNA maturation: RNA polymerization without a nucleic acid template | journal = Current Biology | volume = 14 | issue = 20 | pages = R883–R885 | date = October 2004 | pmid = 15498478 | doi = 10.1016/j.cub.2004.09.069 | doi-access = free | bibcode = 2004CBio...14.R883W }}</ref> In the case of [[miRNA|micro RNA (miRNA)]], miRNAs are first transcribed as primary transcripts or pri-miRNA with a cap and poly-A tail and processed to short, 70-nucleotide stem-loop structures known as pre-miRNA in the cell nucleus by the enzymes [[Drosha]] and [[Pasha (protein)|Pasha]]. After being exported, it is then processed to mature miRNAs in the cytoplasm by interaction with the endonuclease [[Dicer]], which also initiates the formation of the [[RNA-induced silencing complex|RNA-induced silencing complex (RISC)]], composed of the [[Argonaute]] protein.

Even snRNAs and snoRNAs themselves undergo series of modification before they become part of functional RNP complex.<ref>{{cite journal | vauthors = Bratkovič T, Božič J, Rogelj B | title = Functional diversity of small nucleolar RNAs | journal = Nucleic Acids Research | volume = 48 | issue = 4 | pages = 1627–1651 | date = February 2020 | pmid = 31828325 | pmc = 7038934 | doi = 10.1093/nar/gkz1140 }}</ref> This is done either in the nucleoplasm or in the specialized compartments called [[cajal body|Cajal bodies]].<ref>{{cite journal | vauthors = Nizami Z, Deryusheva S, Gall JG | title = The Cajal body and histone locus body | journal = Cold Spring Harbor Perspectives in Biology | volume = 2 | issue = 7 | pages = a000653 | date = July 2010 | pmid = 20504965 | pmc = 2890199 | doi = 10.1101/cshperspect.a000653 }}</ref> Their bases are methylated or pseudouridinilated by a group of [[Small Cajal body-specific RNA|small Cajal body-specific RNAs (scaRNAs)]], which are structurally similar to snoRNAs.<ref>{{cite journal | vauthors = Darzacq X, Jády BE, Verheggen C, Kiss AM, Bertrand E, Kiss T | title = Cajal body-specific small nuclear RNAs: a novel class of 2'-O-methylation and pseudouridylation guide RNAs | journal = The EMBO Journal | volume = 21 | issue = 11 | pages = 2746–2756 | date = June 2002 | pmid = 12032087 | pmc = 126017 | doi = 10.1093/emboj/21.11.2746 }}</ref>

===RNA export===
{{main|Nuclear transport}}
In eukaryotes most mature RNA must be exported to the cytoplasm from the [[cell nucleus|nucleus]]. While some RNAs function in the nucleus, many RNAs are transported through the [[nuclear pore]]s and into the [[cytosol]].<ref name="K2007">{{cite journal | vauthors = Köhler A, Hurt E | title = Exporting RNA from the nucleus to the cytoplasm | journal = Nature Reviews. Molecular Cell Biology | volume = 8 | issue = 10 | pages = 761–773 | date = October 2007 | pmid = 17786152 | doi = 10.1038/nrm2255 | s2cid = 10836137 }}</ref> Export of RNAs requires association with specific proteins known as exportins. Specific exportin molecules are responsible for the export of a given RNA type. mRNA transport also requires the correct association with [[Exon junction complex|Exon Junction Complex]] (EJC), which ensures that correct processing of the mRNA is completed before export. In some cases RNAs are additionally transported to a specific part of the cytoplasm, such as a [[synapse]]; they are then towed by [[motor protein]]s that bind through linker proteins to specific sequences (called "zipcodes") on the RNA.<ref name="Jambhekar2007">{{cite journal | vauthors = Jambhekar A, Derisi JL | title = Cis-acting determinants of asymmetric, cytoplasmic RNA transport | journal = RNA | volume = 13 | issue = 5 | pages = 625–642 | date = May 2007 | pmid = 17449729 | pmc = 1852811 | doi = 10.1261/rna.262607 }}</ref>

===Translation===
{{main|Translation (biology)}}
For some non-coding RNA, the mature RNA is the final gene product.<ref name="Amaral2008">{{cite journal | vauthors = Amaral PP, Dinger ME, Mercer TR, Mattick JS | title = The eukaryotic genome as an RNA machine | journal = Science | volume = 319 | issue = 5871 | pages = 1787–1789 | date = March 2008 | pmid = 18369136 | doi = 10.1126/science.1155472 | s2cid = 206511756 | bibcode = 2008Sci...319.1787A }}</ref> In the case of messenger RNA (mRNA) the RNA is an information carrier coding for the synthesis of one or more proteins. mRNA carrying a single protein sequence (common in eukaryotes) is [[monocistronic]] whilst mRNA carrying multiple protein sequences (common in prokaryotes) is known as [[polycistronic]].

[[File:Ribosome mRNA translation en.svg|300px|thumb|right|alt=Ribosome translating messenger RNA to chain of amino acids (protein).|During the translation, tRNA charged with amino acid enters the ribosome and aligns with the correct mRNA triplet. Ribosome then adds amino acid to growing protein chain.]]
Every mRNA consists of three parts: a 5′ untranslated region (5′UTR), a protein-coding region or [[open reading frame]] (ORF), and a 3′ untranslated region (3′UTR). The coding region carries information for protein synthesis encoded by the [[genetic code]] to form triplets. Each triplet of nucleotides of the [[coding region]] is called a [[codon]] and corresponds to a binding site complementary to an anticodon triplet in transfer RNA. Transfer RNAs with the same anticodon sequence always carry an identical type of [[amino acid]]. Amino acids are then chained together by the [[ribosome]] according to the order of triplets in the coding region. The ribosome helps transfer RNA to bind to messenger RNA and takes the amino acid from each transfer RNA and makes a structure-less protein out of it.<ref name="Hansen2003">{{cite journal | vauthors = Hansen TM, Baranov PV, Ivanov IP, Gesteland RF, Atkins JF | title = Maintenance of the correct open reading frame by the ribosome | journal = EMBO Reports | volume = 4 | issue = 5 | pages = 499–504 | date = May 2003 | pmid = 12717454 | pmc = 1319180 | doi = 10.1038/sj.embor.embor825 }}</ref><ref name="Berk2007">{{cite journal | vauthors = Berk V, Cate JH | title = Insights into protein biosynthesis from structures of bacterial ribosomes | journal = Current Opinion in Structural Biology | volume = 17 | issue = 3 | pages = 302–309 | date = June 2007 | pmid = 17574829 | doi = 10.1016/j.sbi.2007.05.009 }}</ref> Each mRNA molecule is translated into many protein molecules, on average ~2800 in mammals.<ref>{{cite journal | vauthors = Schwanhäusser B, Busse D, Li N, Dittmar G, Schuchhardt J, Wolf J, Chen W, Selbach M | title = Global quantification of mammalian gene expression control | journal = Nature | volume = 473 | issue = 7347 | pages = 337–342 | date = May 2011 | pmid = 21593866 | doi = 10.1038/nature10098 | s2cid = 205224972 | bibcode = 2011Natur.473..337S | url = http://edoc.mdc-berlin.de/11664/1/11664oa.pdf }}</ref><ref name="Schwanhaeusser2011">{{cite journal | vauthors = Schwanhäusser B, Busse D, Li N, Dittmar G, Schuchhardt J, Wolf J, Chen W, Selbach M | title = Corrigendum: Global quantification of mammalian gene expression control | journal = Nature | volume = 495 | issue = 7439 | pages = 126–127 | date = March 2013 | pmid = 23407496 | doi = 10.1038/nature11848 | doi-access = free | bibcode = 2013Natur.495..126S }}</ref>

In prokaryotes translation generally occurs at the point of transcription (co-transcriptionally), often using a messenger RNA that is still in the process of being created. In eukaryotes translation can occur in a variety of regions of the cell depending on where the protein being written is supposed to be. Major locations are the [[cytoplasm]] for soluble cytoplasmic proteins and the membrane of the [[endoplasmic reticulum]] for proteins that are for export from the cell or insertion into a cell [[lipid bilayer|membrane]]. Proteins that are supposed to be produced at the endoplasmic reticulum are recognised part-way through the translation process. This is governed by the [[signal recognition particle]]—a protein that binds to the ribosome and directs it to the endoplasmic reticulum when it finds a [[signal peptide]] on the growing (nascent) amino acid chain.<ref name="Hegde2008">{{cite journal | vauthors = Hegde RS, Kang SW | title = The concept of translocational regulation | journal = The Journal of Cell Biology | volume = 182 | issue = 2 | pages = 225–232 | date = July 2008 | pmid = 18644895 | pmc = 2483521 | doi = 10.1083/jcb.200804157 }}</ref>

===Folding===
{{main|Protein folding}}
[[Image:Protein folding.png|thumb|right|300px|alt=Process of protein folding.|Protein before (left) and after (right) folding]]

Each [[protein]] exists as an unfolded [[polypeptide]] or random coil when translated from a sequence of [[mRNA]] into a linear chain of [[amino acid]]s. This polypeptide lacks any developed three-dimensional structure (the left hand side of the neighboring figure). The polypeptide then folds into its characteristic and functional [[protein structure|three-dimensional structure]] from a [[random coil]].<ref name=Alberts>{{cite book | vauthors = Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walters P | title =Molecular Biology of the Cell | edition = Fourth | publisher =Garland Science| year =2002 | location =New York and London | chapter =The Shape and Structure of Proteins |chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK26830/ | isbn =978-0-8153-3218-3 | author-link =Bruce Alberts}}</ref> Amino acids interact with each other to produce a well-defined three-dimensional structure, the folded protein (the right hand side of the figure) known as the [[native state]]. The resulting three-dimensional structure is determined by the amino acid sequence ([[Anfinsen's dogma]]).<ref name="Anfinsen">{{cite journal | vauthors = Anfinsen CB | title = The formation and stabilization of protein structure | journal = The Biochemical Journal | volume = 128 | issue = 4 | pages = 737–749 | date = July 1972 | pmid = 4565129 | pmc = 1173893 | doi = 10.1042/bj1280737 | author-link = Christian B. Anfinsen }}</ref>

The correct three-dimensional structure is essential to function, although some parts of functional proteins [[Intrinsically disordered proteins|may remain unfolded]].<ref>{{cite book|vauthors = Berg JM,Tymoczko JL, (([[Lubert Stryer]]; Web content by Neil D. Clarke))|title=Biochemistry|publisher=W. H. Freeman|location=San Francisco |year=2002 |isbn=978-0-7167-4684-3 |chapter=3. Protein Structure and Function |chapter-url= https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=stryer%5Bbook%5D+AND+215168%5Buid%5D&rid=stryer.chapter.280}}</ref> Failure to fold into the intended shape usually produces inactive proteins with different properties including toxic [[prion]]s. Several [[neurodegenerative]] and other [[disease]]s are believed to result from the accumulation of ''misfolded'' proteins.<ref name="Selkoe:03">{{cite journal | vauthors = Selkoe DJ | title = Folding proteins in fatal ways | journal = Nature | volume = 426 | issue = 6968 | pages = 900–904 | date = December 2003 | pmid = 14685251 | doi = 10.1038/nature02264 | s2cid = 6451881 | bibcode = 2003Natur.426..900S }}</ref> Many [[allergy|allergies]] are caused by the folding of the proteins, for the immune system does not produce antibodies for certain protein structures.<ref>{{cite book | vauthors = Alberts B, Bray D, Hopkin K, Johnson A, Lewis J, Raff M, Roberts K, Walter P | chapter = Protein Structure and Function | title = Essential Cell Biology | edition = 3rd | location = New York | publisher = Garland Science, Taylor and Francis Group, LLC | year = 2010 | pages = 120–170 |isbn=978-0-8153-4129-1}}</ref>

Enzymes called [[Chaperone (protein)|chaperone]]s assist the newly formed protein to attain ([[protein folding|fold]] into) the 3-dimensional structure it needs to function.<ref name="Hebert2007">{{cite journal | vauthors = Hebert DN, Molinari M | title = In and out of the ER: protein folding, quality control, degradation, and related human diseases | journal = Physiological Reviews | volume = 87 | issue = 4 | pages = 1377–1408 | date = October 2007 | pmid = 17928587 | doi = 10.1152/physrev.00050.2006 | url = https://works.bepress.com/cgi/viewcontent.cgi?article=1021&context=daniel_hebert }}</ref> Similarly, RNA chaperones help RNAs attain their functional shapes.<ref name="Russell2008">{{cite journal | vauthors = Russell R | title = RNA misfolding and the action of chaperones | journal = Frontiers in Bioscience | volume = 13 | issue = 13 | pages = 1–20 | date = January 2008 | pmid = 17981525 | pmc = 2610265 | doi = 10.2741/2557 }}</ref> Assisting protein folding is one of the main roles of the endoplasmic reticulum in eukaryotes.

===Translocation===
Secretory proteins of eukaryotes or prokaryotes must be translocated to enter the secretory pathway. Newly synthesized proteins are directed to the eukaryotic Sec61 or prokaryotic SecYEG translocation channel by [[signal peptide]]s. The efficiency of protein secretion in eukaryotes is very dependent on the [[signal peptide]] which has been used.<ref name="pmid23124363">{{cite journal | vauthors = Kober L, Zehe C, Bode J | title = Optimized signal peptides for the development of high expressing CHO cell lines | journal = Biotechnology and Bioengineering | volume = 110 | issue = 4 | pages = 1164–1173 | date = April 2013 | pmid = 23124363 | doi = 10.1002/bit.24776 | s2cid = 449870 }}</ref>

===Protein transport===
Many proteins are destined for other parts of the cell than the cytosol and a wide range of signalling sequences or [[Signal peptide|(signal peptides)]] are used to direct proteins to where they are supposed to be.<ref>{{cite journal | vauthors = Lu J, Wu T, Zhang B, Liu S, Song W, Qiao J, Ruan H | title = Types of nuclear localization signals and mechanisms of protein import into the nucleus | journal = Cell Communication and Signaling | volume = 19 | issue = 1 | pages = 60 | date = May 2021 | pmid = 34022911 | pmc = 8140498 | doi = 10.1186/s12964-021-00741-y | doi-access = free }}</ref><ref>{{cite journal | vauthors = Lang S, Nguyen D, Bhadra P, Jung M, Helms V, Zimmermann R | title = Signal Peptide Features Determining the Substrate Specificities of Targeting and Translocation Components in Human ER Protein Import | journal = Frontiers in Physiology | volume = 13 | pages = 833540 | date = 2022-07-11 | pmid = 35899032 | pmc = 9309488 | doi = 10.3389/fphys.2022.833540 | doi-access = free }}</ref> In prokaryotes this is normally a simple process due to limited compartmentalisation of the cell.<ref>{{cite journal | vauthors = Murat D, Byrne M, Komeili A | title = Cell biology of prokaryotic organelles | journal = Cold Spring Harbor Perspectives in Biology | volume = 2 | issue = 10 | pages = a000422 | date = October 2010 | pmid = 20739411 | pmc = 2944366 | doi = 10.1101/cshperspect.a000422 }}</ref> However, in eukaryotes there is a great variety of different targeting processes to ensure the protein arrives at the correct organelle.<ref name=":0" />

Not all proteins remain within the cell and many are exported, for example, [[digestive enzymes]], [[hormone]]s and [[extracellular matrix]] proteins. In eukaryotes the export pathway is well developed and the main mechanism for the export of these proteins is translocation to the endoplasmic reticulum, followed by transport via the [[Golgi apparatus]].<ref name="Moreau2007">{{cite journal | vauthors = Moreau P, Brandizzi F, Hanton S, Chatre L, Melser S, Hawes C, Satiat-Jeunemaitre B | title = The plant ER-Golgi interface: a highly structured and dynamic membrane complex | journal = Journal of Experimental Botany | volume = 58 | issue = 1 | pages = 49–64 | year = 2007 | pmid = 16990376 | doi = 10.1093/jxb/erl135 | doi-access = free }}</ref><ref name="Prudovsky2008">{{cite journal | vauthors = Prudovsky I, Tarantini F, Landriscina M, Neivandt D, Soldi R, Kirov A, Small D, Kathir KM, Rajalingam D, Kumar TK | title = Secretion without Golgi | journal = Journal of Cellular Biochemistry | volume = 103 | issue = 5 | pages = 1327–1343 | date = April 2008 | pmid = 17786931 | pmc = 2613191 | doi = 10.1002/jcb.21513 }}</ref>

=== Protein Degradation ===
Protein degradation is a major regulatory mechanism of gene expression<ref>{{Cite journal |last=Schwanhäusser |first=Björn |last2=Busse |first2=Dorothea |last3=Li |first3=Na |last4=Dittmar |first4=Gunnar |last5=Schuchhardt |first5=Johannes |last6=Wolf |first6=Jana |last7=Chen |first7=Wei |last8=Selbach |first8=Matthias |date=2011-05-19 |title=Global quantification of mammalian gene expression control |url=https://www.nature.com/articles/nature10098 |journal=Nature |language=en |volume=473 |issue=7347 |pages=337–342 |doi=10.1038/nature10098 |issn=0028-0836}}</ref><ref>{{Cite journal |last=McShane |first=Erik |last2=Selbach |first2=Matthias |date=2022-10-06 |title=Physiological Functions of Intracellular Protein Degradation |url=https://www.annualreviews.org/content/journals/10.1146/annurev-cellbio-120420-091943 |journal=Annual Review of Cell and Developmental Biology |language=en |volume=38 |issue=1 |pages=241–262 |doi=10.1146/annurev-cellbio-120420-091943 |issn=1081-0706}}</ref> and contributes substantially for shaping proteomes, especially of tissues and cells that do not grow very fast.<ref name=":1">{{Citation |last=Leduc |first=Andrew |title=Protein degradation and growth dependent dilution substantially shape mammalian proteomes |date=2025-02-12 |url=http://biorxiv.org/lookup/doi/10.1101/2025.02.10.637566 |access-date=2025-02-16 |language=en |doi=10.1101/2025.02.10.637566 |last2=Slavov |first2=Nikolai|pmc=11844506 }}</ref> Protein degradation is a highly regulated processes, which results in significant and context dependent variation in degradation rates between proteins as well as for the same protein across cell types and tissue types. This variation can contribute about 40 % of the variance of protein levels across slowly growing tissues, with the remaining 60 % likely coming from protein synthesis, including transcription and translation as explained above.<ref name=":1" />