Gene regulation
Gene regulation is a complex biological process that dictates when and how genes are expressed, ultimately influencing the production of proteins within a cell. This process begins with transcription, where a specific segment of DNA is copied into messenger RNA (mRNA) by an enzyme known as RNA polymerase. In prokaryotes, transcription and translation occur simultaneously, allowing for rapid protein synthesis, while in eukaryotes, mRNA is processed in the nucleus before being translated in the cytoplasm. Key elements in gene regulation include promoters, which are sequences of DNA that signal the start of transcription, and various regulatory sequences like enhancers and silencers, which modulate gene expression levels.
Transcription factors, proteins that assist RNA polymerase, play a crucial role in recognizing these regulatory elements. Eukaryotic genes undergo additional modifications, such as the addition of a 5' cap and a poly-A tail, which protect the mRNA and facilitate its transport to ribosomes for translation. The structure of chromatin, or the complex of DNA and proteins in chromosomes, also affects gene regulation by influencing accessibility to the transcriptional machinery. Overall, gene regulation is essential for cellular function and adaptation, impacting various biological processes and responses to environmental stimuli.
Gene regulation
Categories: Cellular biology; genetics
When a gene is expressed, one strand of that gene’s double helical deoxyribonucleic acid (DNA) is copied, in the process of transcription, by an enzyme called RNA (ribonucleic acid) polymerase to make a messenger RNA (mRNA). The mRNA then associates with a ribosome (formed by specific ribosomal RNAs and proteins), where the nucleic acid base sequence is read, to produce the corresponding protein in a process called translation. A section of three nucleotides, called a codon, codes for one amino acid. Small RNA molecules called transfer RNAs (tRNAs) carry specific amino acids to the ribosome during translation. That amino acid is added to the growing polypeptide chain when the anticodon part of the tRNA pairs with a codon of the mRNA being translated.
Prokaryotic vs. Eukaryotic Regulation
Prokaryotes (Bacteria and Archaea) and eukaryotes (all other life-forms, including plants and animals) carry out transcription and translation in very similar ways, but there are some differences. The RNA polymerases and ribosomes differ between the two types of cell. In a prokaryote, such as a bacterium, translation of an mRNA can begin as soon as the first part of the mRNA molecule has been made from the DNA template. This is said to be “coupled” transcription and translation. In the eukaryotic cell, mRNA is transcribed in the nucleus and crosses the nuclear envelope to go to the cytoplasm, where the mRNA is translated into proteins on ribosomes.
Promoters
Transcription begins at a promoter, which is a DNA sequence at the start of a gene that tells the RNA polymerase where to start transcribing the DNA to make mRNA. The promoter includes the site where transcription begins (the initiation site) as well as sequences upstream, which are not transcribed. In eukaryotes, RNA polymerase II recognizes a DNA sequence called the TATA box (because it contains many thymine (T) and adenine (A) bases) that is about thirty nucleotides upstream of the initiation site. Another element often found in promoters is the CAAT box (which includes cytosine (C) bases).
Other regulatory elements include enhancer sequences, which can be in either orientation in the chromosome and far from the coding region of the gene. Enhancers may be involved in regulating the specificity of expression of a gene in a particular tissue or organ. Silencer sequences are structurally similar to enhancers but function to decrease gene expression. Other proteins, called transcription factors, aid the RNA polymerase in locating and binding to the promoter. The DNA-binding domains of eukaryotic transcription factors may have one of several types of structural motifs, such as a helix-turn-helix structure, a zinc finger (a cysteine- and histidine-rich region of the protein that complexes zinc), or a leucine zipper. Once the polymerase binds, it separates the two strands of DNA at the initiation site, and transcription begins. Transcription ends at a termination site on the DNA. In eukaryotes, a common termination sequence is AATAAA.
Other Regulatory Elements
Genes with related functions often have similar regulatory elements. A number of environmentally induced genes in plants contain the G-box with the sequence 5'CCACGTGG3'. Genes that respond to light, ultraviolet radiation, cold, and drought have the G-box and at least one additional regulatory element. For example, genes that respond to the hormone abscisic acid also have an abscisic acid-responsive element.
Role of Chromatin
The chromosomes of eukaryotes consist of unique, single-copy genes among a complex pattern of repetitive DNAs. In addition, there are DNAs in organelles outside the nucleus, such as mitochondria and chloroplasts. Each eukaryotic chromosome contains a single long DNA molecule that is coiled, folded, and compacted by its interaction with chromosomal proteins called histones. This complex of DNA with chromosomal proteins and chromosomal RNAs is chromatin. The DNA of higher eukaryotes appears to be organized into looped domains of chromatin by attachment to a nuclear scaffold. The loops are anchored at matrix-attachment regions that function in the structural organization of the DNA and may increase transcription of certain genes by promoting the formation of a less-condensed chromatin.
Transcription and mRNA Processing in Eukaryotes
In the eukaryote, as mRNA makes its way from the nucleus to the ribosomes in the cytoplasm, the mRNA molecule is modified (RNA processing). Both ends of the mRNA are altered. The 5' end (the end that is first formed during transcription) is capped by the addition of a modified guanine (G) residue (7-methylguanosine). The 5' cap protects the mRNA from degradation by nucleases and serves as a signal for the attachment of small ribosomal subunits to the mRNA. While still in the nucleus, the 3' end of the mRNA is also modified. An enzyme adds thirty to two hundred adenine nucleotides (called a poly-A tail). The poly-A tail inhibits mRNA degradation and may aid in mRNA transport to the cytoplasm.
In addition, many eukaryotic mRNAs are spliced in a cut-and-paste process in which a large part of the RNA molecule initially synthesized is removed. The parts of the DNA that code for the RNA that will be discarded are the intervening sequences, or introns. The DNA that codes for the parts of the RNA that will be translated are exons.
Bibliography
Buchanan, Bob B., Wilhalm Gruissem, and Russell L. Jones. Biochemistry and Molecular Biology of Plants. Rockville, Md.: American Society of Plant Physiologists, 2000. A comprehensive textbook. Includes illustrations, photos, sources, and index.
Calladine, C. R., and Horace R. Drew. Understanding DNA: The Molecule and How It Works. San Diego: Academic Press, 1997. Focuses on the structure of DNA. Includes figures, exercises, and index.
Griffiths, Anthony J. F., et al. An Introduction to Genetic Analysis. New York: W. H. Freeman, 2000. An upper-level college textbook. Includes CD-ROM, illustrations, problem sets with solutions, glossary, and index.
Lewin, Benjamin. Genes VII. New York: Oxford University Press, 2000. This standard college-level textbook contains individual chapters on messenger RNA, protein, synthesis, transcription, and chromosomes. Includes illustrations, glossary, and index.
Lodish, Harvey, et al. Molecular Cell Biology. New York: W. H. Freeman, 2000. Comprehensive text with an experimental emphasis. Includes CD, figures, and index.