Primary transcript

For example, a precursor messenger RNA (pre-mRNA) is a primary transcript that becomes a messenger RNA (mRNA) after processing.

Primary Transcript Production

The steps contributing to the production of the primary transcript within cells involves a series of interactions to initiate the transcription of DNA in 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 initiate the transcription process in a cell's nucleus, DNA double helices are unwound and hydrogen bonds connecting compatible nucleic acids of DNA are broken to produce two disconnected DNA single strands.^[1] The DNA template to be used for transcription of the single-stranded primary transcript mRNA is then bound by an RNA polymerase at the promoter region.^[2] In eukaryotes, three kinds of RNA-- rRNA, tRNA, and mRNA-- may be produced based on the activity of three distinct RNA polymerases, whereas, in prokaryotes, only one RNA polymerase exists to create any and all kinds of RNA molecules.^[3] RNA polymerase II of eukaryotes transcribes the primary transcript mRNA from the antisense DNA template in the 5' to 3' direction, and the newly synthesized mRNA is complimentary to this template strand of DNA.^[4] RNA polymerase II constructs the primary transcript using a set of four specific ribonucleoside monophosphate residues (AMP, CMP, GMP, and UMP) that are added continuously to the 3' hydroxyl group on the 3' end of the growing mRNA.^[5] Studies of primary transcripts produced by RNA polymerase II reveal that a given primary transcript averages 7000 nucleotides in length, some growing as long as 20,000 nucleotides in length.^[6] Inclusion of the exon and intron components within primary transcript sequences explain for the extreme size disparity between larger primary transcripts and smaller, modified mRNA ready for translation into protein.

Regulation of Primary Transcript Production

A number of factors contribute to the activation and inhibition of transcription and therefore regulate the production of primary transcript mRNA from a given DNA template. Activation of RNA polymerase activity to produce primary transcripts is often controlled by other DNA sequence elements called enhancers. The transcription factors that bind to enhancer regions of DNA recruit enzymes that alter nucleosome components to be either more or less accessible to RNA polymerase. The unique combinations of transcription factors that bind to enhancer DNA regions determine whether or not the gene that enhancer interacts with becomes activated or not. ^[7] The activation of transcription by RNA polymerase depends on whether or not the transcription elongation complex, itself consisting of a variety of transcription factors, can induce RNA polymerase to dissociate from the Mediator complex connecting an enhancer region to the promoter.^[8] Inhibition of RNA polymerase activity can also be regulated by DNA elements called silencers. Like enhancers, silencers may be located at locations farther up or downstream from the genes they regulate. These DNA sequences bind to factors that contribute to the destabilization of the initiation complex required to activate RNA polymerase, and therefore inhibit transcription.^[9]

Histone modification by transcription factors is another key regulatory factor for transcription by RNA polymerase. In general, factors that lead to histone acetylation activate transcription while factors that cause histone deacetylation inhibit transcription.^[10] Acetylation of histones induces repulsion between negative components in the coiled DNA, opening up nucleosomes for RNA polymerase access. Deacetylation of histones favors more tightly coiled nucleosomes, inhibiting RNA polymerase access. In addition to acetylation patterns of histones, methylation patterns at promoter regions of DNA can regulate access RNA polymerase can have to a desired template. RNA polymerase is often incapable of synthesizing a primary transcript if the targeted gene's promoter region contains specific methylated cytosines— residues that hinder binding of transcription-activating factors and recruit other enzymes to stabilize a tightly bound nucleosome structure, excluding access to RNA polymerase.^[11]

References

1. Strachan, T. "Human Molecular Genetics 2nd Edition". NCBI. New York: Wiley-Liss.
2. Alberts, B. "Molecular Biology of the Cell 3rd Edition". NCBI. New York: Garland Science.
3. Griffiths, AJF. "An Introduction to Genetic Analysis". NCBI. New York: W.H. Freeman.
4. Strachan, T. "Human Molecular Genetics 2nd Edition". NCBI. New York: Wiley-Liss.
5. Strachan, T. "Human Molecular Genetics 2nd Edition". NCBI. New York: Wiley-Liss.
6. Alberts, B. "Molecular Biology of the Cell 3rd Edition". NCBI. New York: Garland Science.
7. Gilbert, Scott (2014). Developmental Biology 10th Edition. Sunderland, MA: Sinauer Associates Inc. p. 38.
8. Gilbert, Scott (2014). Developmental Biology 10th Edition. Sunderland, MA: Sinauer Associates Inc. p. 39.
9. Brown, T.A. "Genomes 2nd Edition". NCBI. Oxford: Wiley-Liss.
10. Lodish, H. "Molecular Cell Biology". NCBI. New York: W.H. Freeman.
11. Gilbert, Scott (2014). Developmental Biology 10th Edition. Sunderland, MA: Sinauer Associates Inc. p. 50.