How is Gene Expression Regulated?

Several Mechanisms are Integrated to Keep Protein Level

Feb 8, 2010
Asaf Peer

A Scheme of a Regulatory Network - Asaf Peer

Proteins are the key factors taking actions in living cells. Their level should be kept constant. This is done by incorporating several modes of regulation.

A living cell contains three major biological molecules: DNA, RNA and protein. The variety of available proteins is huge and is as small as several hundreds in some bacteria and up to tens of thousands in higher eukaryotes. The number of copies of each protein should be tightly kept and any deviation from the optimal amount in a given time-point could lead to the destruction of the cell or some diseases.

From Transcription to Translation and a Protein

The DNA holds all the genetic and some of the epigenetic information. All the proteins are encoded on the DNA and are expressed when needed, in the desired amount. The DNA is transcribed into RNA and the RNA is then translated into a protein. The protein might not be functional and in several cases should be activated using several other mechanisms. Regulation of each step, as well as of the stability of the mature protein is used to keep its desired level.

Transcription of DNA into RNA requires the RNA-polymerase complex. This complex is recruited to the DNA in regions that should be transcribed. Some proteins, known as transcription factors, direct the RNA-polymerase to the site where transcription should take place. Several copies of the same factor can direct multiple copies of the RNA-polymerase to distinct locations on the DNA, leading to the transcription of several genes. This way one transcription factor can activate multiple genes that are required for a certain purpose.

After the RNA transcript is produced it should be translated into a protein. This process also requires a complex, named ribosome. The ribosome binds to the RNA message and translates the message to a protein according to the genetic code. Translation could be enhanced or reduced using some mechanisms including proteins and other RNA, molecules such as small-RNAs, micro-RNAs and si-RNAs. The stability of the RNA message is also important and could be altered using the above factors.

Mature Proteins are Regulated as Well

After a protein is produced, it might not be active. Some proteins require some modifications such as ribosylation or phosphorylation, that is, the addition of a ribose or a phosphate groups to some residue. The protein can turned on and off using modifications, making the activation very cheap in energy and transient.

A protein is a complex molecule, exposed to other chemicals and enzymes, and is naturally degraded. The degradation of a protein is a natural phenomenon but it can also be regulated. When a protein is no longer needed it can be marked for destruction and degraded using some other enzymes.

Tradeoffs Between Modes of Regulation

A protein level can be regulated in each point of the path between DNA and an active protein. Preventing the transcription of a protein is on one hand cheap on energy since the protein is not produced but on the other hand, if the protein is suddenly needed in the cell it will take a lot of time to produce it.

Regulating the rate of translation and the stability of the messenger RNA can lead to a bit more expensive regulation but the protein levels could be kept more tightly. Controlling the protein stability or activity using modifications is the most expensive option since the protein should be constantly produced but it is very transient and tightly controlled.

The cell is a complex system in which every bolt and nut should properly function in a timely manner. Controlling the level of each protein is done using several mechanisms with benefits and drawbacks for each.

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