Post-transcriptional modification 3239191 222421609 2008-06-29T07:16:52Z Narayanese 1324750 {{MolBioGeneExp}} {{for|Differential post-transcriptional changes|Post-transcriptional regulation}} '''Post-transcriptional modification''' is a process in [[cell biology]] by which, in [[eukaryotic cells]], [[RNA|primary transcript RNA]] is converted into [[RNA|mature RNA]]. A notable example is the conversion of [[precursor messenger RNA]] into [[mature messenger RNA|mature]] [[messenger RNA]] (mRNA), which includes [[splicing (genetics)|splicing]] and occurs prior to [[protein synthesis]]. This process is vital for the correct [[translation]] of the [[genome]]s of eukaryotes as the human primary RNA transcript that is produces as a result of [[transcription (biology)|transcription]] contains both [[exons]], which are coding sections of the primary RNA transcript and [[introns]], which are the non coding sections of the primary RNA transcript.<ref name="Stryer836">{{Harvnb|Berg|Tymoczko|Stryer|2007|Ref=CITEREFBergTymoczkoStryer2008|p=836}}</ref> ==''' mRNA processing''' == The pre-mRNA molecule undergoes three main modifications. These modifications are [[5' cap]]ping, 3' [[polyadenylation]], and [[RNA splicing]], which occur in the [[nucleus]] of the cell before the RNA is [[translation (biology)|translated]].<ref name="Stryer841">{{Harvnb|Berg|Tymoczko|Stryer|2007|Ref=CITEREFBergTymoczkoStryer2008|p=841}}</ref> ===5' Processing=== {{main|5' cap}} ==== Capping ==== Capping of the pre-mRNA involves the addition of '''7-methylguanosine (m<sup>7</sup>G)''' to the 5' end. In order to achieve this, the terminal 5' phosphate requires removal, which is done by the aid of a '''[[phosphatase]] enzyme'''. The enzyme '''guanosyl transferase''' then catalyses the reaction which produces the [[diphosphate]] 5' end. The diphosphate 5' prime end then attacks the α phosphorus atom of a [[GTP]] molecule in order to add the [[guanine]] residue in a 5'5' triphosphate link. The enzyme '''[[S-adenosyl methionine]]''' then methylates the guanine ring at the N-7 position. This type of cap, with just the (m<sup>7</sup>G) in position is called a '''cap 0 structure'''. The [[ribose]] of the adjacent [[nucleotide]] may also be methylated to give a '''cap 1'''. Methylation of nucleotides downstream of the RNA molecule produce '''cap 2''', '''cap 3''' structures and so on. In these cases the methyl groups are added to the 2' OH groups of the ribose sugar. The cap protects the 5' end of the primary RNA transcript from attack by [[ribonucleases]] that have specificity to the 3'5' [[phosphodiester bonds]]. <ref name="CITEREFBiochemistry1">{{Harvnb|Hames|Hooper|2006|Ref=CITEREFHamesHopper2008|p=221}}</ref> ===3' Processing=== {{main|Polyadenylation}} ====Cleavage and Polyadenylation==== The pre-mRNA processing at the 3' end of the RNA molecule involves cleavage of its 3' end and then the addition of about 200 [[adenine]] residues to form a [[poly(A) tail]]. The cleavage and adenylation reactions occur if a [[polyadenylation|polyadenylation signal sequence]] (5'- AAUAAA-3') is located near the 3' end of the pre-mRNA molecule, which is followed by another sequence, which is usually '''(5'-CA-3')'''. The second signal is the site of cleavage. A '''GU-rich sequence''' is also usually present further downstream on the pre-mRNA molecule. After the synthesis of the sequence elements, two multisubunit [[protien]]s called [[cleavage and polyadenylation specificity factor]] (CPSF) and [[cleavage stimulation factor]] (CStF) are transferred from [[RNA Polymerase II]] to the RNA molecule. The two factors bind to the sequence elements. A protein complex forms which contains additional cleavage factors and the enzyme [[Polyadenylate Polymerase]] (PAP). This complex cleaves the RNA between the polyadenylation sequence and the GU-rich sequence at the cleavage site marked by the (5'-CA-3') sequences. Poly(A) polymerase then adds about 200 adenine units to the new 3' end of the RNA molecule using [[ATP]] as a precursor. As the poly(A) tails is synthesised, it binds multiple copies of poly(A) binding protein, which protects the 3'end from ribonuclease digestion.<ref name="CITEREFBiochemistry1">{{Harvnb|Hames|Hooper|2006|Ref=CITEREFHamesHopper2008|p=225}}</ref> [[Image:Conserved Polyadenylation Sequence.svg|center|700px]] === Splicing === {{main|RNA splicing}} RNA splicing is the process by which [[intron]]s, regions of RNA that do not code for protein, are removed from the pre-mRNA and the remaining [[exon]]s connected to re-form a single continuous molecule. Although most RNA splicing occurs after the complete synthesis and end-capping of the pre-mRNA, transcripts with many exons can be spliced co-transcriptionally.<ref name="Lodish_2007">{{cite book | author = Lodish HF, Berk A, Kaiser C, Krieger M, Scott MP, Bretscher A, Ploegh H, Matsudaira PT | title = Molecular Cell .Biology | publisher = WH Freeman | location = San Francisco | year = 2007 | pages = | isbn = 0-7167-7601-4 | oclc = | doi = | chapter = Chapter 8: Post-transcriptional Gene Control }}</ref> The splicing reaction is catalyzed by a large protein complex called the [[spliceosome]] assembled from proteins and [[small nuclear RNA]] molecules that recognize [[splice site]]s in the pre-mRNA sequence. Many pre-mRNAs, including those encoding [[antibody|antibodies]], can be spliced in multiple ways to produce different mature mRNAs that encode different [[primary structure|protein sequences]]. This process is known as [[alternative splicing]], and allows production of a large variety of proteins from a limited amount of DNA. ==Citations== {{reflist|2}} ==References== #{{Harvard reference |surname1 = Berg |given1 = Jeremy M. |surname2 = Tymoczko |given2 = John L. |surname3 = Stryer |given3 = Lubert |authorlink3 = Lubert Stryer |title = Biochemistry |date = 2007 |place = [[New York]] |edition = 6 |publisher = WH Freeman & Co. |id = ISBN 0-71676-766-X }} #{{Harvard reference |surname1 = Hames |given1 = David |surname2 = Hooper |given2 = Nigel |title = Instant Notes Biochemistry |date = 2006 |place = [[Leeds]] |edition = 3 |publisher = Taylor and Francis |id = ISBN 0-4153-6778-6 }} ==See also== *[[messenger RNA]] *[[translation (genetics)|translation]] *[[RNA editing]] ==External links== * {{MeshName|Post-Transcriptional+RNA+Modification}} {{Protein biosynthesis}} {{Post transcriptional modification}} [[Category:RNA]] [[de:Posttranskriptionale Modifizierung]] [[fr:Modification post-transcriptionnelle]] [[pl:Obróbka posttranskrypcyjna]] [[vi:Chế biến mRNA]]