Simple and Complex Transcription Unit

  • In this simple and complex transcription unit post we have briefly explained about monocistronic mRNAs produced by eukaryotic genes and introns simple and complex transcription unit in eukaryotic genomes.
  • In molecular terms, a gene commonly is defined as the entire nucleic acid sequence that is necessary for the synthesis of a functional gene product (polypeptide or RNA). According to this definition, a gene includes more than the nucleotides encoding the amino acid sequence of a protein, referred to as the coding region.
  • A gene also includes all the DNA sequences required for synthesis of a particular RNA transcript. In eukaryotic genes, transcription-control regions known as enhancers can lie 50 kb or more from the coding region.
  • Other critical noncoding regions in eukaryotic genes are the sequences that specify 3’ cleavage and polyadenylation, known as poly (A) sites, and splicing of primary RNA transcripts, known as splice sites. Mutations in these RNA-processing signals prevent expression of a functional mRNA and thus of the encoded polypeptide.
  • Although most genes are transcribed into mRNAs, which encode proteins, clearly some DNA sequences are transcribed into RNAs that do not encode proteins (e.g., tRNAs and rRNAs).
  • However, because the DNA that encodes tRNAs and rRNAs can cause specific phenotypes when it is mutated, these DNA regions generally are referred to as tRNA and rRNA genes, even though the final products of these genes are RNA molecules and not proteins. Many other RNA molecules are also transcribed from non-protein-coding genes.

Monocistronic mRNAs

  • Many bacterial mRNAs are polycistronic; that is, a single mRNA molecule (e.g., the mRNA encoded by the trpoperon) includes the coding region for several proteins that function together in a biological process. In contrast, most eukaryotic mRNAs are monocistronic; that is, each mRNA molecule encodes a single protein. This difference between polycistronic and monocistronic mRNAs correlates with a fundamental difference in their translation.
  • Within a bacterial polycistronic mRNA a ribosome binding site is located near the start site for each of the protein coding regions, or cistrons, in the mRNA. Translation initiation can begin at any of these multiple internal sites, producing multiple proteins.
  • In most eukaryotic mRNAs, however, the 5’-cap structure directs ribosome binding, and translation begins at the closest AUG start codon. As a result, translation begins only at this site. In many cases, the primary transcripts of eukaryotic protein-coding genes are processed into a single type of mRNA, which is translated to give a single type of polypeptide.
  • Unlike bacterial and yeast genes, which generally lack introns, most genes in multicellular animals and plants contain introns, which are removed during RNA processing. In many cases, the introns in a gene are considerably longer than the exons.
  • For instance, of the ≈50,000 base pairs composing many human genes encoding average-size proteins, more than 95 percent are present in introns and noncoding 5’ and 3’ regions. Many large proteins in higher organisms have repeated domains and are encoded by genes consisting of repeats of similar exons separated by introns of variable length.
  • An example of this is fibronectin, a component of the extracellular matrix that is encoded by a gene containing multiple copies of three types of exons.

Simple and Complex Transcription Unit

  • The cluster of genes that form a bacterial operon comprises a single transcription unit, which is transcribed from a particular promoter into a single primary transcript. In other words, genes and transcription units often are distinguishable in prokaryotes.
  • In contrast, most eukaryotic genes and transcription units generally are identical, and the two terms commonly are used interchangeably. Eukaryotic transcription units, however, are classified into two types, depending on the fate of the primary transcript.
  • The primary transcript produced from a simple transcription unit is processed to yield a single type of mRNA, encoding a single protein. Mutations in exons, introns, and transcription-control regions all may influence expression of the protein encoded by a simple transcription unit.
  • In the case of complex transcription units, which are quite common in multicellular organisms, the primary RNA transcript can be processed in more than one way, leading to formation of mRNAs containing different exons. Each mRNA, however, is monocistronic, being translated into a single polypeptide, with translation usually initiating at the first AUG in the mRNA. Multiple mRNAs can arise from a primary transcript in three ways.
  • Use of different splice sites, producing mRNAs with the same 5’ and 3’ exons but different internal exons. Figure shows one example of this type of alternative RNA processing, exon skipping. Use of alternative poly(A) sites, producing mRNAs that share the same 5’ exons but have different 3’ exons.
  • Use of alternative promoters, producing mRNAs that have different 5’ exons and common 3’ exons. A gene expressed selectively in two or more types of cells is often transcribed from distinct cell-type-specific promoters.
  • Examples of all three types of alternative RNA processing occur during sexual differentiation in Drosophila. Commonly, one mRNA is produced from a complex transcription unit in some cell types, and an alternative mRNA is made in other cell types.
  • For example, differences in RNA splicing of the primary fibronectin transcript in fibroblasts and hepatocytes determines whether or not the secreted protein includes domains that adhere to cell surfaces.
  • The relationship between a mutation and a gene is not always straightforward when it comes to complex transcription units. A mutation in the control region or in an exon shared by alternative mRNAs will affect all the alternative proteins encoded by a given complex transcription unit. On the other hand, mutations in an exon present in only one of the alternative mRNAs will affect only the protein encoded by that mRNA.
  • However, in the complex transcription unit shown in Figure Complex transcription unit (middle), mutations d and e would complement each other in a genetic complementation test, even though they occur in the same gene.
  • This is because a chromosome with mutation d can express a normal protein encoded by mRNA2 and a chromosome with mutation e can express a normal protein encoded by mRNA1.
  • However, a chromosome with mutation c in an exon common to both mRNAs would not complement either mutation d or e. In other words, mutation c would be in the same complementation groups as mutations d and e, even though d and e themselves would not be in the same complementation group.

Further Readings