Introduction

This chapter discusses the mechanisms that exist to influence gene transcription more directly and gives idea about exons and introns. To understand these mechanisms, a basic understanding of the parts that make up a gene and how those parts can influence gene expression is necessary.

Exons and Introns

Eukaryotic genes are different from prokaryotic genes in that they are not co-linear with their peptide products. The single nucleic acid strand of eukaryotic mRNA comes from non-contiguous regions on the chromosome. Exons are the regions of DNA that code for parts of a protein, while introns are the intervening sequences between exons that have no connection with the amino acid sequence of the protein.

Human β-Globin Gene

The human β-globin gene encodes part of the hemoglobin protein of red blood cells and consists of the following elements:

Promoter Region

• The promoter region is where RNA polymerase II binds to initiate transcription.
• The human β-globin gene has a promoter region that extends from 95 to 26 base pairs before the transcription initiation site.
• Some promoters have a TATA-box DNA sequence, which binds the TATA-binding protein that helps anchor RNA polymerase II to the promoter.

Transcription Initiation Site

• The transcription initiation site for human β-globin is ACATTTG.
• This site is often called the cap sequence, as it codes for the addition of a modified nucleotide “cap” at the 5′ end of the RNA.
• The cap sequence begins the first exon.

5′ UTR

• The 5′ UTR, also known as the leader sequence, is the sequence of 50 base pairs intervening between the initiation points of transcription and translation.
• This region can determine the rate of translation initiation.

Translation Initiation Site

• The translation initiation site for human β-globin is ATG.
• This codon is located 50 base pairs after the transcription initiation site and starts the translation of the mRNA.

Protein-Encoding Exons

• The first exon in the human β-globin gene contains 90 base pairs coding for amino acids 1-30 of the protein.
• The second exon contains 222 base pairs coding for amino acids 31-104.
• The third exon contains 126 base pairs coding for amino acids 105-146 of the protein.

Introns

• Introns are the intervening sequences between exons that have no coding sequences for the protein.
• The structure of introns is important in enabling the RNA to be processed into mRNA and exit the nucleus.

Translation Termination Codon

• The translation termination codon in the human β-globin gene is TAA.
• When a ribosome encounters this codon, it dissociates, and the protein is released.

3′ UTR

• The 3′ UTR is not translated into protein but is transcribed.
• This region includes a polyA tail, which confers stability on the mRNA, allows it to exit the nucleus, and enables translation into protein.

Transcription Termination Sequence

• Transcription continues beyond the 3′ UTR for about 1000 nucleotides before being terminated.

Nuclear RNA (nRNA)

• The original transcription product is called nuclear RNA or heterogeneous nuclear RNA.
• This RNA contains the cap sequence, 5′ UTR, exons, introns, and 3′ UTR.
• Both ends of these transcripts are modified before they leave the nucleus.