The Proteome: It's a bit more complex than any of us would like

The biology 101 description of protein synthesis usually goes as follows:

RNA polymerase transcribes DNA into messenger RNA (mRNA).

mRNA is bound by a ribosome.

Bada bing bada boom.

Protein!

Except, there’s a lot of stuff that happens in-between the creation of mRNA and the translation of that message by a ribosome.

And much like DNA transcription, there are MULTIPLE levels of regulation that occur on the cellular level to make sure that the right proteins are made at the right time!

With that in mind, it's also important to note that mRNA abundance is not directly correlated with protein abundance for approximately 30% of genes.

So, just having mRNA around doesn’t necessarily mean that a protein is going to be made!

What the heck is going on here?

Translation Initiation: This is the first and arguably most regulated step! For an mRNA to be translated it has to be found and bound by a ribosome. Except ribosomes aren’t just bouncing around the cytoplasm (or endoplasmic reticulum) looking for naked mRNAs! Ribosomes are actually recruited by other other factors like the cap binding protein complex eIF4F (eukaryotic translation initiation factors) and the Poly-A Binding Protein (PABP) that binds the mRNA tail. These two protein complexes circularize the mRNA. That way, when a ribosome gets to the end, it’s back at the beginning to start all over again! However, this circularization process is highly regulated and even when a ribosome does find its way to one of these RNAs, there’s no guarantee that it will actually be translated! The ribosome itself is regulated, and for it to start the process of scanning for the translation initiation codon (the start site) it must be bound by a methionine loaded tRNA!

Translation Elongation: This is the phase of translation where all of the amino acids are added to the growing protein chain. However, how quickly those amino acids are added can be regulated and this can affect how much protein is made from any one message!

Location, Location, Location: Whether an mRNA is translated into protein depends a lot on where it is! This makes sense and is an important factor in the regulation of translation. If an RNA is no longer needed, it can be bound by factors that bring it to a processing body (P-body) for decay. These are little areas within the cytoplasm where RNAs are decapped and chopped up by nucleases. But if a cell doesn’t want to destroy an RNA, it can save it for later by moving it to a stress granule (like a p-body, just with less chopping!). This usually happens during stressful situations and translation can be completed when conditions improve.

microRNAs: These are small pieces of RNA that bind to the 3’-UTR (Untranslated Region) of an mRNA and mark it for death by the RNA-induced Silencing Complex (RISC). If an RNA is disappeared, it can’t be translated!