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The steps contributing to the production of primary transcripts involve a series of molecular interactions that initiate transcription of DNA within a cell's nucleus. Based on the needs of a given cell, certain DNA sequences are transcribed to produce a variety of RNA products to be translated into functional proteins for cellular use. To initiate the transcription process in a cell's nucleus, DNA double helices are unwound and [[hydrogen bond]]s connecting compatible nucleic acids of DNA are broken to produce two unconnected single DNA strands.<ref name="StrachanRead2004">{{cite book| vauthors = Strachan T, Read AP |title=Human Molecular Genetics 3|url=https://books.google.com/books?id=g4hC63UrPbUC|date=January 2004|publisher=Garland Science|isbn=978-0-8153-4184-0|pages=16–17}}</ref> One strand of the DNA template is used for transcription of the single-stranded primary transcript mRNA. This DNA strand is bound by an [[RNA polymerase]] at the [[promoter (genetics)|promoter]] region of the DNA.<ref name="Alberts3rd">{{cite book| vauthors = Alberts B |title=Molecular Biology of the Cell |chapter=RNA Synthesis and RNA Processing | edition = 3rd |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK28319/| via = NCBI |date=1994 |publisher=New York: Garland Science}}</ref>
[[File:Transcription.jpg|thumb|Transcription of DNA by RNA polymerase to produce primary transcript]]
In eukaryotes, three kinds of RNA—[[rRNA]], [[tRNA]], and mRNA—are produced based on the activity of three distinct RNA polymerases, whereas, in [[prokaryotes]], only one RNA polymerase exists to create all kinds of RNA molecules.<ref>{{cite web| vauthors = Griffiths AJ |title=An Introduction to Genetic Analysis |url= https://www.ncbi.nlm.nih.gov/books/NBK21853/|archive-url= https://web.archive.org/web/20200108205509/https://www.ncbi.nlm.nih.gov/books/NBK21853/|url-status= dead|archive-date= January 8, 2020|work=NCBI|date=2000 |publisher=New York: W.H. Freeman}}</ref> RNA polymerase II of eukaryotes transcribes the primary transcript, a transcript destined to be processed into mRNA, from the [[antisense]] DNA template in the 5' to 3' direction, and this newly synthesized primary transcript is complementary to the antisense strand of DNA.<ref name="StrachanRead2004" /> RNA polymerase II constructs the primary transcript using a set of four specific [[ribonucleoside]] monophosphate residues ([[adenosine monophosphate]] (AMP), [[cytidine monophosphate]] (CMP), [[guanosine monophosphate]] (GMP), and [[uridine monophosphate]] (UMP)) that are added continuously to the 3' hydroxyl group on the 3' end of the growing mRNA.<ref name="StrachanRead2004" />
Studies of primary transcripts produced by RNA polymerase II reveal that an average primary transcript is 7,000 [[nucleotide]]s in length, with some growing as long as 20,000 nucleotides in length.<ref name="Alberts3rd"/> The inclusion of both [[exon]] and [[intron]] sequences within primary transcripts explains the size difference between larger primary transcripts and smaller, mature mRNA ready for translation into protein.{{cn|date=July 2024}}
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===Transcription stress===
[[DNA damage (naturally occurring)|DNA damages]] arise in each cell, every day, with the number of damages in each cell reaching tens to hundreds of thousands, and such DNA damages can impede primary transcription.<ref name = Milano2024>{{cite journal |vauthors=Milano L, Gautam A, Caldecott KW |title=DNA damage and transcription stress |journal=Mol Cell |volume=84 |issue=1 |pages=70–79 |date=January 2024 |pmid=38103560 |doi=10.1016/j.molcel.2023.11.014 |url=|doi-access=free }} {{CC-notice|cc=by4}}</ref> The process of [[gene expression]] itself is a source of endogenous DNA damages resulting from the susceptibility of single-stranded DNA to damage.<ref name = Milano2024/> Other sources of DNA damage are conflicts of the primary transcription machinery with the [[DNA replication]] machinery, and the activity of certain enzymes such as [[topoisomerase]]s and [[base excision repair]] enzymes. Even though these processes are tightly regulated and are usually accurate, occasionally they can make mistakes and leave behind DNA breaks that drive [[chromosomal rearrangement]]s or [[cell death]].<ref name = Milano2024/>
==RNA processing==
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In [[HeLa cell]]s, spliceosome groups on pre-mRNA were found to form within [[nuclear speckles]], with this formation being temperature-dependent and influenced by specific RNA sequences. Pre-mRNA targeting and splicing factor loading in speckles were critical for spliceosome group formation, resulting in a speckled pattern.<ref>{{cite journal | title = Prespliceosomal assembly on microinjected precursor mRNA takes place in nuclear speckles | journal = Molecular Biology of the Cell | volume = 12 | issue = 2 | pages = 393–406 | date = February 2001 | pmid = 11179423 | doi = 10.1091/mbc.12.2.393 | citeseerx = 10.1.1.324.8865 | pmc = 30951 | vauthors = Melčák I, Melčáková Š, Kopsky V, Večeřová J, Raška I }}</ref>
Recruiting pre-mRNA to nuclear speckles significantly increased splicing efficiency and protein levels, indicating that proximity to speckles enhances splicing efficiency.<ref>{{cite journal | title = Genome organization around nuclear speckles drives mRNA splicing efficiency. | journal = Nature | volume = 629 | issue = 8014 | pages = 1165–1173 | date = May 2024 | pmid = 38720076 | pmc = 11164319 | doi = 10.1038/s41586-024-07429-6
==Related diseases==
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