 | Thisis missing information about sections for RNA other than mRNA. Please expand the to include this information. Further details may exist on thetalk page.(October 2020) |
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Transcriptional modification orco-transcriptional modification is a set of biological processes common to mosteukaryotic cells by which anRNAprimary transcript is chemically altered followingtranscription from agene to produce a mature, functional RNA molecule that can then leave thenucleus and perform any of a variety of different functions in the cell.[1] There are many types of post-transcriptional modifications achieved through a diverse class of molecular mechanisms.
One example is the conversion of precursormessenger RNA transcripts into mature messenger RNA that is subsequently capable of beingtranslated intoprotein. This process includes three major steps that significantly modify the chemical structure of the RNA molecule: the addition of a5' cap, the addition of a 3'polyadenylated tail, andRNA splicing. Such processing is vital for the correct translation of eukaryoticgenomes because the initial precursor mRNA produced by transcription often contains bothexons (coding sequences) andintrons (non-coding sequences); splicing removes the introns and links the exons directly, while the cap and tail facilitate the transport of the mRNA to aribosome and protect it from molecular degradation.[2]
Post-transcriptional modifications may also occur during the processing of other transcripts which ultimately becometransfer RNA,ribosomal RNA, or any of the other types of RNA used by the cell.
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Capping of the pre-mRNA involves the addition of7-methylguanosine (m7G) to the 5' end. To achieve this, the terminal 5' phosphate requires removal, which is done with the aid of enzymeRNA triphosphatase. The enzymeguanosyl transferase then catalyses the reaction, which produces thediphosphate 5' end. The diphosphate 5' end then attacks the alpha phosphorus atom of aGTP molecule in order to add theguanine residue in a 5'5' triphosphate link. The enzyme(guanine-N7-)-methyltransferase ("cap MTase") transfers a methyl group fromS-adenosyl methionine to the guanine ring.[4] This type of cap, with just the (m7G) in position is called a cap 0 structure. Theribose of the adjacentnucleotide 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 byribonucleases that have specificity to the 3'5'phosphodiester bonds.[5]
The pre-mRNA processing at the 3' end of the RNA molecule involves cleavage of its 3' end and then the addition of about 250adenine residues to form apoly(A) tail. The cleavage and adenylation reactions occur primarily if apolyadenylation 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') and is the site of cleavage. AGU-rich sequence is also usually present further downstream on the pre-mRNA molecule. More recently, it has been demonstrated that alternate signal sequences such as UGUA upstream off the cleavage site can also direct cleavage and polyadenylation in the absence of the AAUAAA signal. These two signals are not mutually independent, and often coexist. After the synthesis of the sequence elements, several multi-subunitproteins are transferred to the RNA molecule. The transfer of these sequence specific binding proteinscleavage and polyadenylation specificity factor (CPSF), Cleavage Factor I (CF I) andcleavage stimulation factor (CStF) occurs fromRNA Polymerase II. The three factors bind to the sequence elements. The AAUAAA signal is directly bound by CPSF. For UGUA dependent processing sites, binding of the multi protein complex is done by Cleavage Factor I (CF I). The resultant protein complex formed contains additional cleavage factors and the enzymePolyadenylate 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 usingATP as a precursor. As the poly(A) tail is synthesized, it binds multiple copies ofpoly(A)-binding protein, which protects the 3'end from ribonuclease digestion by enzymes including theCCR4-Not complex.[5]
RNA splicing is the process by whichintrons, regions of RNA that do not code for proteins, are removed from the pre-mRNA and the remainingexons connected to re-form a single continuous molecule. Exons are sections of mRNA which become "expressed" or translated into a protein. They are the coding portions of a mRNA molecule.[6] 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.[7] The splicing reaction is catalyzed by a large protein complex called thespliceosome assembled from proteins andsmall nuclear RNA molecules that recognizesplice sites in the pre-mRNA sequence. Many pre-mRNAs, including those encodingantibodies, can be spliced in multiple ways to produce different mature mRNAs that encode differentprotein sequences. This process is known asalternative splicing, and allows production of a large variety of proteins from a limited amount of DNA.
Histones H2A, H2B, H3 and H4 form the core of anucleosome and thus are calledcore histones. Processing of core histones is done differently because typical histone mRNA lacks several features of other eukaryotic mRNAs, such as poly(A) tail and introns. Thus, such mRNAs do not undergo splicing and their 3' processing is done independent of most cleavage and polyadenylation factors. Core histone mRNAs have a specialstem-loop structure at 3-prime end that is recognized by astem–loop binding protein and a downstream sequence, called histone downstream element (HDE) that recruitsU7 snRNA.Cleavage and polyadenylation specificity factor 73 cuts mRNA between stem-loop and HDE[8]
Histone variants, such asH2A.Z or H3.3, however, have introns and are processed as normal mRNAs including splicing and polyadenylation.[8]
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