This is missing information about sections for RNA other than mRNA. Please expand the to include this information. Further details may exist on the talk page.(October 2020)
Transcriptional modification or co-transcriptional modification is a set of biological processes common to most eukaryotic cells by which an RNAprimary transcript is chemically altered following transcription from a gene to produce a mature, functional RNA molecule that can then leave the nucleus 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 precursor messenger RNA transcripts into mature messenger RNA that is subsequently capable of being translated into protein. This process includes three major steps that significantly modify the chemical structure of the RNA molecule: the addition of a 5' cap, the addition of a 3' polyadenylated tail, and RNA splicing. Such processing is vital for the correct translation of eukaryotic genomes because the initial precursor mRNA produced by transcription often contains both exons (coding sequences) and introns (non-coding sequences); splicing removes the introns and links the exons directly, while the cap and tail facilitate the transport of the mRNA to a ribosome and protect it from molecular degradation.[2]
Post-transcriptional modifications may also occur during the processing of other transcripts which ultimately become transfer RNA, ribosomal RNA, or any of the other types of RNA used by the cell.
Capping of the pre-mRNA involves the addition of 7-methylguanosine (m7G) to the 5' end. To achieve this, the terminal 5' phosphate requires removal, which is done with the aid of enzyme RNA triphosphatase. The enzyme guanosyl transferase then catalyses the reaction, which produces the diphosphate 5' end. The diphosphate 5' end then attacks the alpha phosphorus atom of a GTP molecule in order to add the guanine residue in a 5'5' triphosphate link. The enzyme (guanine-N7-)-methyltransferase ("cap MTase") transfers a methyl group from S-adenosyl methionine to the guanine ring.[4] This type of cap, with just the (m7G) 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.[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 250 adenine residues to form a poly(A) tail. The cleavage and adenylation reactions occur primarily 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') and is the site of cleavage. A GU-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. It is important to understand that these two signals are not mutually independent and often coexist. After the synthesis of the sequence elements, several multi-subunit proteins are transferred to the RNA molecule. The transfer of these sequence specific binding proteins cleavage and polyadenylation specificity factor (CPSF), Cleavage Factor I (CF I) and cleavage stimulation factor (CStF) occurs from RNA 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 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) tail is synthesized, it binds multiple copies of poly(A)-binding protein, which protects the 3'end from ribonuclease digestion by enzymes including the CCR4-Not complex.[5]
RNA splicing is the process by which introns, regions of RNA that do not code for proteins, are removed from the pre-mRNA and the remaining exons 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 the spliceosome assembled from proteins and small nuclear RNA molecules 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.
Histones H2A, H2B, H3 and H4 form the core of a nucleosome and thus are called core 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 special stem-loop structure at 3-prime end that is recognized by a stem–loop binding protein and a downstream sequence, called histone downstream element (HDE) that recruits U7 snRNA. Cleavage and polyadenylation specificity factor 73 cuts mRNA between stem-loop and HDE[8]
Histone variants, such as H2A.Z or H3.3, however, have introns and are processed as normal mRNAs including splicing and polyadenylation.[8]
^ abShafee, Thomas; Lowe, Rohan (2017). "Eukaryotic and prokaryotic gene structure". WikiJournal of Medicine. 4 (1). doi:10.15347/wjm/2017.002. ISSN 2002-4436.
^Yamada-Okabe T, Mio T, Kashima Y, Matsui M, Arisawa M, Yamada-Okabe H (November 1999). "The Candida albicans gene for mRNA 5-cap methyltransferase: identification of additional residues essential for catalysis". Microbiology. 145 ( Pt 11) (11): 3023–33. doi:10.1099/00221287-145-11-3023. PMID 10589710.
^Lodish HF, Berk A, Kaiser C, Krieger M, Scott MP, Bretscher A, Ploegh H, Matsudaira PT (2007). "Chapter 8: Post-transcriptional Gene Control". Molecular Cell .Biology. San Francisco: WH Freeman. ISBN978-0-7167-7601-7.
^ abMarzluff WF, Wagner EJ, Duronio RJ (November 2008). "Metabolism and regulation of canonical histone mRNAs: life without a poly(A) tail". Nature Reviews. Genetics. 9 (11): 843–54. doi:10.1038/nrg2438. PMC2715827. PMID 18927579.
Sun WJ, Li JH, Liu S, Wu J, Zhou H, Qu LH, Yang JH (January 2016). "RMBase: a resource for decoding the landscape of RNA modifications from high-throughput sequencing data". Nucleic Acids Research. 44 (D1): D259-65. doi:10.1093/nar/gkv1036. PMC4702777. PMID 26464443.
Machnicka MA, Milanowska K, Osman Oglou O, Purta E, Kurkowska M, Olchowik A, Januszewski W, Kalinowski S, Dunin-Horkawicz S, Rother KM, Helm M, Bujnicki JM, Grosjean H (January 2013). "MODOMICS: a database of RNA modification pathways--2013 update". Nucleic Acids Research. 41 (Database issue): D262-7. doi:10.1093/nar/gks1007. PMC3531130. PMID 23118484.
Post-Transcriptional+RNA+Modification at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
August 23, 2023
post, transcriptional, modification, this, missing, information, about, sections, other, than, mrna, please, expand, include, this, information, further, details, exist, talk, page, october, 2020, transcriptional, modification, transcriptional, modification, b. This is missing information about sections for RNA other than mRNA Please expand the to include this information Further details may exist on the talk page October 2020 Transcriptional modification or co transcriptional modification is a set of biological processes common to most eukaryotic cells by which an RNA primary transcript is chemically altered following transcription from a gene to produce a mature functional RNA molecule that can then leave the nucleus 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 precursor messenger RNA transcripts into mature messenger RNA that is subsequently capable of being translated into protein This process includes three major steps that significantly modify the chemical structure of the RNA molecule the addition of a 5 cap the addition of a 3 polyadenylated tail and RNA splicing Such processing is vital for the correct translation of eukaryotic genomes because the initial precursor mRNA produced by transcription often contains both exons coding sequences and introns non coding sequences splicing removes the introns and links the exons directly while the cap and tail facilitate the transport of the mRNA to a ribosome and protect it from molecular degradation 2 Post transcriptional modifications may also occur during the processing of other transcripts which ultimately become transfer RNA ribosomal RNA or any of the other types of RNA used by the cell Contents 1 mRNA processing 1 1 5 processing 1 1 1 Capping 1 2 3 processing 1 2 1 Cleavage and polyadenylation 1 3 Introns Splicing 1 4 Histone mRNA processing 2 See also 3 References 4 Further readingmRNA processing Edit Regulatory sequence Regulatory sequence Enhancer silencer Promoter 5 UTR Open reading frame 3 UTR Enhancer silencer Proximal Core Start Stop Terminator Transcription DNA Exon Exon Exon Intron Intron Post transcriptionalmodification Pre mRNA Protein coding region 5 cap Poly A tail Translation MaturemRNA Protein The structure of a eukaryotic protein coding gene Regulatory sequence controls when and where expression occurs for the protein coding region red Promoter and enhancer regions yellow regulate the transcription of the gene into a pre mRNA which is modified to remove introns light grey and add a 5 cap and poly A tail dark grey The mRNA 5 and 3 untranslated regions blue regulate translation into the final protein product 3 Polycistronic operon Regulatory sequence Regulatory sequence Enhancer Enhancer silencer silencer Operator Promoter 5 UTR ORF ORF UTR 3 UTR Start Start Stop Stop Terminator Transcription DNA RBS RBS Protein coding region Protein coding region mRNA Translation Protein The structure of a prokaryotic operon of protein coding genes Regulatory sequence controls when expression occurs for the multiple protein coding regions red Promoter operator and enhancer regions yellow regulate the transcription of the gene into an mRNA The mRNA untranslated regions blue regulate translation into the final protein products 3 5 processing Edit Main article 5 cap Capping Edit Capping of the pre mRNA involves the addition of 7 methylguanosine m7G to the 5 end To achieve this the terminal 5 phosphate requires removal which is done with the aid of enzyme RNA triphosphatase The enzyme guanosyl transferase then catalyses the reaction which produces the diphosphate 5 end The diphosphate 5 end then attacks the alpha phosphorus atom of a GTP molecule in order to add the guanine residue in a 5 5 triphosphate link The enzyme guanine N7 methyltransferase cap MTase transfers a methyl group from S adenosyl methionine to the guanine ring 4 This type of cap with just the m7G 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 5 3 processing Edit Cleavage and polyadenylation Edit Main article 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 250 adenine residues to form a poly A tail The cleavage and adenylation reactions occur primarily 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 and is the site of cleavage A GU 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 It is important to understand that these two signals are not mutually independent and often coexist After the synthesis of the sequence elements several multi subunit proteins are transferred to the RNA molecule The transfer of these sequence specific binding proteins cleavage and polyadenylation specificity factor CPSF Cleavage Factor I CF I and cleavage stimulation factor CStF occurs from RNA 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 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 tail is synthesized it binds multiple copies of poly A binding protein which protects the 3 end from ribonuclease digestion by enzymes including the CCR4 Not complex 5 Introns Splicing Edit Main article RNA splicing RNA splicing is the process by which introns regions of RNA that do not code for proteins are removed from the pre mRNA and the remaining exons 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 the spliceosome assembled from proteins and small nuclear RNA molecules 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 Histone mRNA processing Edit Main article Histone Histones H2A H2B H3 and H4 form the core of a nucleosome and thus are called core 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 special stem loop structure at 3 prime end that is recognized by a stem loop binding protein and a downstream sequence called histone downstream element HDE that recruits U7 snRNA Cleavage and polyadenylation specificity factor 73 cuts mRNA between stem loop and HDE 8 Histone variants such as H2A Z or H3 3 however have introns and are processed as normal mRNAs including splicing and polyadenylation 8 See also EditPost translational modification RNA editing RNA SeqReferences Edit Kiss T July 2001 Small nucleolar RNA guided post transcriptional modification of cellular RNAs The EMBO Journal 20 14 3617 22 doi 10 1093 emboj 20 14 3617 PMC 125535 PMID 11447102 Berg Tymoczko amp Stryer 2007 p 836harvnb error no target CITEREFBergTymoczkoStryer2008 help a b Shafee Thomas Lowe Rohan 2017 Eukaryotic and prokaryotic gene structure WikiJournal of Medicine 4 1 doi 10 15347 wjm 2017 002 ISSN 2002 4436 Yamada Okabe T Mio T Kashima Y Matsui M Arisawa M Yamada Okabe H November 1999 The Candida albicans gene for mRNA 5 cap methyltransferase identification of additional residues essential for catalysis Microbiology 145 Pt 11 11 3023 33 doi 10 1099 00221287 145 11 3023 PMID 10589710 a b Hames amp Hooper 2006 p 221harvnb error no target CITEREFHamesHopper2008 help Biology Mgraw hill education 2014 pp 241 242 ISBN 978 981 4581 85 1 Lodish HF Berk A Kaiser C Krieger M Scott MP Bretscher A Ploegh H Matsudaira PT 2007 Chapter 8 Post transcriptional Gene Control Molecular Cell Biology San Francisco WH Freeman ISBN 978 0 7167 7601 7 a b Marzluff WF Wagner EJ Duronio RJ November 2008 Metabolism and regulation of canonical histone mRNAs life without a poly A tail Nature Reviews Genetics 9 11 843 54 doi 10 1038 nrg2438 PMC 2715827 PMID 18927579 Further reading EditBerg JM Tymoczko JL Stryer L 2007 Biochemistry 6 ed New York WH Freeman amp Co ISBN 978 0 7167 6766 4 Hames D Hooper N 2006 Instant Notes Biochemistry p 767 ISBN 978 0 415 36778 3 PMID 11098183 a href Template Cite book html title Template Cite book cite book a journal ignored help Sun WJ Li JH Liu S Wu J Zhou H Qu LH Yang JH January 2016 RMBase a resource for decoding the landscape of RNA modifications from high throughput sequencing data Nucleic Acids Research 44 D1 D259 65 doi 10 1093 nar gkv1036 PMC 4702777 PMID 26464443 Machnicka MA Milanowska K Osman Oglou O Purta E Kurkowska M Olchowik A Januszewski W Kalinowski S Dunin Horkawicz S Rother KM Helm M Bujnicki JM Grosjean H January 2013 MODOMICS a database of RNA modification pathways 2013 update Nucleic Acids Research 41 Database issue D262 7 doi 10 1093 nar gks1007 PMC 3531130 PMID 23118484 Cantara WA Crain PF Rozenski J McCloskey JA Harris KA Zhang X Vendeix FA Fabris D Agris PF January 2011 The RNA Modification Database RNAMDB 2011 update Nucleic Acids Research 39 Database issue D195 201 doi 10 1093 nar gkq1028 PMC 3013656 PMID 21071406 Post Transcriptional RNA Modification at the U S National Library of Medicine Medical Subject Headings MeSH Retrieved from https en wikipedia org w index php title Post transcriptional modification amp oldid 1160485407, wikipedia, wiki, book, books, library,
