Gene expression and the regulation of genes

Gene expression and the regulation of genes

A gene that is expressed, simply means that it is active. If a gene is a set of instructions, gene expression simply means that the instructions are being read and acted upon by cellular machinery. The result of gene expression is a functional protein, or phenotype.

The cellular machine that 'reads' the DNA sequence coding for a gene is called DNA polymerase. As it speeds along the DNA strand, the DNA polymerase machine produces a single strand of RNA, called an mRNA transcript. These transcripts are subsequently 'read' by ribosomes, which in turn produce an amino acid chain which then is folded to make a functional protein. The functional protein is the resulting phenotype of gene expression.

A great proportion of our DNA is made up of non-coding sequences in-between the gene sequences. This used to be called junk DNA and thought to be useless. In the last decade or two, it has become evident that the sequences in between genes are just as important as the genes themselves. It also gets read and transcribed into much shorter RNA sequences, called non-coding RNA (ncRNA). MicroRNA and siRNAs are examples of these non-coding transcripts. These ncRNAs play a crucial role in regulating the gene expression: The process of making a protein from a gene can be thwarted by ncRNAs! By attaching, or more specifically complementary base-pairing with the mRNA transcript, they stop the translation of that mRNA into protein. Due to regulation of ncRNAs, gene expression does not always end in a corresponding phenotype.  In other words, even though the gene is active, being read, transcribed into mRNA and in the process of becoming a functional protein, ncRNAs can get in the way and stop the process and make sure the protein is not made!

This activation and deactivation of genes is happening in cells all the time, because feedback networks are often at odds with each other when they give instructions to a cell. If all is well, the balance of this tug-of-war of on and off switches creates a healthy cell that functions well. When out of balance, a cell may for example produce far too much VEGF (Vascular Endothelial Growth Factor). Over-production of VEGF stimulates the growth of blood vessels in the carcinogenic process of angiogenesis, in cancer.

Non-coding RNAs have a critical role in regulating gene expression. The study of how these small, ncRNA transcripts play out to control gene activity is part of a wider field of study called Epigenetics. Epigenetics encompasses other ways in which genes are regulated, namely methylation and acetylation, and these methods will be explained in a future blog.

Further reading and information

Patients: Video on how instructions on the DNA end up creating a functional protein Link to video; and here's another video (highly recommended!) which explains how this process can be regulated. And, if you're feeling a bit more technical and have a science background, here's a great video explaining the function of all the different non-coding RNAs.

Practitioners: Burdick et al., 2012, Expression of E-Selectin ligands on Circulating Tumor Cells: cross-regulation of cancer stem cell regulatory pathways? Frontiers in Oncology: 2; 103 Link to free full text. And here's a six-minute video about the generation and action of micro-RNAs