In the articles that follow, we’ll examine different forms of eukaryotic gene regulation. That is, we’ll see how the expression of genes in eukaryotes (like us!) can be controlled at various stages, from the availability of DNA to the production of mRNAs to the translation and processing of proteins.Eukaryotic gene expression involves many steps, and almost all of them can be regulated. Different genes are regulated at different points, and it’s not uncommon for a gene (particularly an important or powerful one) to be regulated at multiple steps.
- Chromatin accessibility. The structure of chromatin (DNA and its organizing proteins) can be regulated. More open or “relaxed” chromatin makes a gene more available for transcription.
- Transcription. Transcription is a key regulatory point for many genes. Sets of transcription factor proteins bind to specific DNA sequences in or near a gene and promote or repress its transcription into an RNA.
- RNA processing. Splicing, capping, and addition of a poly-A tail to an RNA molecule can be regulated, and so can exit from the nucleus. Different mRNAs may be made from the same pre-mRNA by alternative splicing.
Stages of eukaryotic gene expression (any of which can be potentially regulated).
- Chromatin structure. Chromatin may be tightly compacted or loose and open.
- Transcription. An available gene (with sufficiently open chromatin) is transcribed to make a primary transcript.
- Processing and export. The primary transcript is processed (spliced, capped, given a poly-A tail) and shipped out of the nucleus.
- mRNA stability. In the cytosol, the mRNA may be stable for long periods of time or may be quickly degraded (broken down).
- Translation. The mRNA may be translated more or less readily/frequently by ribosomes to make a polypeptide.
- Protein processing. The polypeptide may undergo various types of processing, including proteolytic cleavage (snipping off of amino acids) and addition of chemical modifications, such as phosphate groups.
All these steps (if applicable) need to be executed for a given gene for an active protein to be present in the cell.Image based on similar diagrams from Reece et al. ^11start superscript, 1, end superscript and Purves et al. ^22squared
- RNA stability. The lifetime of an mRNA molecule in the cytosol affects how many proteins can be made from it. Small regulatory RNAs called miRNAs can bind to target mRNAs and cause them to be chopped up.
- Translation. Translation of an mRNA may be increased or inhibited by regulators. For instance, miRNAs sometimes block translation of their target mRNAs (rather than causing them to be chopped up).
- Protein activity. Proteins can undergo a variety of modifications, such as being chopped up or tagged with chemical groups. These modifications can be regulated and may affect the activity or behavior of the protein.
Although all stages of gene expression can be regulated, the main control point for many genes is transcription. Later stages of regulation often refine the gene expression patterns that are “roughed out” during transcription.