The regulation of gene ex
In eukaryotes, transcription is driven by three distinct RNA polymerases: RNA polymerase I (RNAPI), RNA polymerase II (RNAPII), and RNA polymerase III (RNAPIII). Although possessing a similar structural design, they transcribe different species of RNA. RNAPI and RNAPIII transcribe genes encoding ribosomal RNA (rRNA), transfer RNA (tRNA), and small nuclear RNA (U6 snRNA), whereas RNAPII is responsible for the transcription of the protein-coding genes, the majority of small nuclear RNAs (snRNAs), and small nucleolar RNAs (snoRNAs). In addition, RNAPII transcribes a wide range of RNA species with no apparent coding potential. These non-coding RNAs include small interfering RNAs (siRNAs), micro-RNAs (miRNAs), cryptic unstable transcripts (CUTs), stable unannotated transcripts (SUTs), Xrn1 stabilized transcripts (XUTs), meiotic unannotated transcripts (MUTs), and Ssu72-restricted transcripts (SRTs). In addition, there are other RNAPII-transcribed non-coding RNA species that do not fall into any of the categories described above. The biological role of many of these non-coding RNAs is not yet clear.
A typical RNA polymerase II transcription cycle begins with the binding of activators upstream of the core promoter, which includes a TATA box and transcription start site. Activator binding leads to the recruitment of adaptor complexes such as SAGA, or Mediator, both of which facilitate binding of general transcription factors (GTFs). RNA polymerase II is positioned at the promoter by a combination of TFIID, TFIIA, and TFIIB to form the closed form of the preinitiation complex (PIC). TFIIH then melts 11-15 bp of DNA to position the single strand template in the RNA polymerase II cleft to initiate RNA synthesis. The carboxy-terminal domain (CTD) of RNA polymerase II is phosphorylated by the TFIIH subunit during the first 30bp of transcription and loses its contacts with GTFs before it proceeds onto the elongation phase. Meanwhile, the phosphorylated CTD begins to recruit the factors that are important for productive elongation and mRNA processing. The termination of transcription, 3’ end processing of the transcript, and release of RNA polymerase II, is precisely coordinated in order to ensure the proper production of the RNA product. RNA polymerase II pauses once it has transcribed the poly(A) track at the 3’ end of the gene, resulting in the recruitment of the termination machinery, including Rtt103, Rat1, Ssu72, and cleavage and polyadenylation factor (CPF).
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