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Factors affecting gene expression

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The available genetic material in an individual or a species is one thing. All cells in the body have the same DNA. Forget that! (no, not really) That's not the fun part. The fun part is how the genome works, and how genes are expressed, if at all. This is what actually keeps life ticking the way it does. This is why we have cells that look different and act differently. This is why your environment and choices can make a difference.


Transcription factors

Transcriptional factors are molecules which can bind DNA and thus initiate transcription. Most of the time these are inactive in the cytoplasm because they have an inhibitor attached to them.

Hormones like oestrogen which are crucial to immunity, bone development, female reproduction, etc. can bind to transcriptional factors and release their inhibitor. Oestrogen crosses the plasma membrane freely as it is lipid-soluble.

This enables the transcriptional factor to migrate from the cytoplasm into the nucleus via the nuclear pore, bind DNA and initiate transcription of specific genes.




RNA splicing

In eukaryotes, genes contain non-coding sequences which must be removed before mRNA is used to produce proteins. These are called introns as opposed to exons which are coding sequences. Splicing therefore is the process of excising (cutting out) introns to be left with mRNA containing purely coding sequence.


This process can result in several different mRNA products from the same DNA sequence. If the introns and exons are arranged differently, the mRNA will code for different amino acids. It's termed alternative splicing.




Since these two possible mRNA products code for different amino acids represented by the different colours (red-yellow-blue versus red-green-blue), the resulting protein after translation of mRNA could function differently. If an enzyme, it may affect its ability to catalyse its reactions, or its efficiency. Equally, the change could not make a difference in another scenario at all.


Epigenetics

In eukaryotes, epigenetics refers to the heritable changes in gene function that do not involve any change to the DNA sequence. This underpins an embryo's ability to differentiate its cells into specialised lineages for different organs and tissues in the adult: skin tissue, muscle tissue, nervous tissue, etc.

Transcription can be inhibited by specific means. A common way is increased DNA methylation. The methyl (CH3) group acts as a tag on the DNA at various locations and prevents transcription that might've occurred otherwise.




Another chemical modification that can induce epigenetic effects and control gene expression is histone deacetylation. Histones hold the DNA chromatin and help to compress it. In its acetylated state, it is relaxed and the DNA can be accessed by transcription machinery. Deacetylation results in the tightening of chromatin around the histones, no longer making the genetic material accessible.




Knowledge of epigenetics can help in addressing various illness including cancer. Controlling gene expression remotely is much easier than having to change the DNA sequence itself. Drugs can act as signals for specific genes to be activated or deactivated. In the case of cancer, it has been shown that cancer cells switch off the genes associated with tumour detection. They also show additional epigenetic anomalies such as histone modifications and deregulation of proteins that bind DNA.




RNA interference (RNAi)

A major component in the regulation of transcription and translation is RNA interference, notably via microRNA (miRNA) and small interfering RNA (siRNA).

miRNA is a sequence complementary to a portion of transcribed mRNA. Upon binding a complex protein, it attaches to the section of target mRNA, thus blocking translation as well as speeding up the eventual breakdown of the mRNA strand.




As for siRNA, it does what it says, it interferes and it's small! What does it interfere with? It interferes with translation by binding to mRNA and cleaving it. This prevents it from being translated in the cytoplasm via tRNA and ribosomes to produce a polypeptide. Therefore the specific gene it codes for is not expressed.





siRNA is a short, double-stranded fragment of RNA which binds and cleaves mRNA through a RISC - RNA-inducing silencing complex. This is the same Dicer processing enzyme and the RISC protein complex involved in the miRNA pathway because miRNA and siRNA share the same machinery after they're synthesised.

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