- Post-transcriptional modification
Post-transcriptional modification is a process in
cell biologyby which, in eukaryotic cells, primary transcript RNA is converted into mature RNA. A notable example is the conversion of precursor messenger RNAinto mature messenger RNA(mRNA), which includes splicing and occurs prior to protein synthesis. This process is vital for the correct translationof the genomes of eukaryotes as the human primary RNA transcript that is produces as a result of 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.Harvnb|Berg|Tymoczko|Stryer|2007|Ref=CITEREFBergTymoczkoStryer2008|p=836]
The pre-mRNA molecule undergoes three main modifications. These modifications are
5' capping, 3' polyadenylation, and RNA splicing, which occur in the cell nucleusbefore the RNA is translated.Harvnb|Berg|Tymoczko|Stryer|2007|Ref=CITEREFBergTymoczkoStryer2008|p=841]
Capping of the pre-mRNA involves the addition of 7-methylguanosine (m7G) to the 5' end. In order to achieve this, the terminal 5' phosphate requires removal, which is done by the aid of a
phosphataseenzyme. The enzyme guanosyl transferase then catalyses the reaction which produces the diphosphate5' end. The diphosphate 5' prime end then attacks the α phosphorus atom of a GTPmolecule in order to add the guanineresidue in a 5'5' triphosphate link. The enzyme S-adenosyl methioninethen methylates the guanine ring at the N-7 position. This type of cap, with just the (m7G) in position is called a cap 0 structure. The riboseof the adjacent nucleotidemay 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 ribonucleasesthat have specificity to the 3'5' phosphodiester bonds. Harvnb|Hames|Hooper|2006|Ref=CITEREFHamesHopper2008|p=221]
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
adenineresidues to form a poly(A) tail. The cleavage and adenylation reactions occur if a 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 protiens called cleavage and polyadenylation specificity factor(CPSF) and cleavage stimulation factor(CStF) are transferred from RNA Polymerase IIto 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 ATPas 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.Harvnb|Hames|Hooper|2006|Ref=CITEREFHamesHopper2008|p=225]
RNA splicing is the process by which
introns, regions of RNA that do not code for protein, are removed from the pre-mRNA and the remaining exons 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.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 ] The splicing reaction is catalyzed by a large protein complex called the spliceosomeassembled from proteins and small nuclear RNAmolecules that recognize splice sites in the pre-mRNA sequence. Many pre-mRNAs, including those encoding antibodies, can be spliced in multiple ways to produce different mature mRNAs that encode different protein sequences. This process is known as alternative splicing, and allows production of a large variety of proteins from a limited amount of DNA.
surname1 = Berg
given1 = Jeremy M.
surname2 = Tymoczko
given2 = John L.
surname3 = Stryer
given3 = Lubert
authorlink3 = Lubert Stryer
title = Biochemistry
date = 2007
edition = 6
publisher = WH Freeman & Co.
id = ISBN 0-71676-766-X
surname1 = Hames
given1 = David
surname2 = Hooper
given2 = Nigel
title = Instant Notes Biochemistry
date = 2006
edition = 3
publisher = Taylor and Francis
id = ISBN 0-4153-6778-6
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