Genetics

How Gene Expression is Regulated



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Every living creature has within its cells a genetic code made of nucleotides on a sugar-phosphate backbone nucleic acid. There are two types of nucleic acids ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). In most living things, the genetic material is DNA. For the sake of simplicity, the genetics applicable to animals is discussed further; bacteria and viruses have more complex and variable genetic assemblies that are easier to understand once the basics are mastered.

Gene expression is the central dogma of biochemistry. In animals, DNA is a double-stranded helix. This is the structure discerned by Watson and Crick in the mid-twentieth century. There are four types of nucleotides that make up the genetic code, two complementary pairs that hold the helix together via hydrogen bonds. Single stranded (separated) DNA is transcribed by the cell's machinery into single stranded RNA, known as messenger RNA (mRNA), in a process called transcription. The mRNA is then translated by additional cell machinery into protein by ribosomes and another type of RNA, transfer RNA (tRNA), reading the strand three nucleotides at a time and constructing a string of amino acids to make the peptide, the building block of proteins. This process is called translation.

The resulting protein, the gene product, is gene expression, though gene expression is sometimes measured on the mRNA level to discern between transcriptional and translational control in the laboratory.Gene regulation is essentially the control a cell exerts over gene expression.

Among the four-nucleotide sequence of DNA are blocks of sequence known as genes. Genes encode particular proteins and are read by the cellular machinery to produce a particular protein, as described above, based on its sequence. Genes are defined by start and stop sequences consisting of three nucleotides (codons). Flanking genes are also untranslated regions and regulatory sequences known as enhancers, silencers, and promoters.

The promoter region of a gene occurs before the start codon and can be short, a few hundred base pairs, or long, several kilobases, depending on the distance to the next gene. Some regulatory sequences even occur within other genes, making the regulation of gene expression very complex to discern and understand for some genes. Within the promoter region, as well as enhancers and silencers, are nucleotide sequences recognized by transcription factors, proteins that bind to a DNA sequence and affect transcription. Some transcription factors increase gene expression for some genes while hindering it for others. Transcriptions factors include hormone response elements, short RNA sequences, ligand binding proteins, and a slew of complexes that can bind to the transcription machinery.

Gene regulation can occur at any of the steps of gene expression. Transcriptional regulation involves transcription factors. Post-transcriptional regulation involves mRNA processing and the transport of mRNA to the cytoplasm for translation. Once mRNA has been transcribed it is spliced to remove nonsense sequences, called introns. The mRNA is also polyadenylated and capped for transportation out of the nucleus. Alterations in the sequence that prevent this process inhibit gene expression because the protein is not made. Sometimes introns are not properly spliced and result an mRNA that cannot be translated properly.

Translational regulation involves ribosome function. Post-translational regulation is dependent on the post-translational modification of the protein. If a protein does not properly fold or is not completed due to ribosomal stalling, it is degraded and gene expression is hindered.

The rate of gene expression is the amount of functional protein that is produced. Various factors at the various stages of the process influence increases and decreases in protein levels, regulating gene expression. Many physiological systems use feedback mechanisms to regulate genes, where the protein produced binds the DNA sequence to limit further production until the levels decrease and more is required. Another variation of this is the binding of hormones to turn genes on or off by binding the regulatory sequences and blocking or aiding the binding of transcriptional machinery, resulting in physiological responses to hormone concentrations at the level of gene expression blood pressure regulation, liver function, additional hormone secretion, neurotransmitter release all dependent on proteins, which are gene products.View a video of the DNA-RNA interaction and speculative research on which came first based on gene regulation experiments.

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