For years, I have used the hypothesis of front-loading to argue that multifunctional, moonlighting proteins would be expected to exist. I explained the logic and provided many examples using the ribosome as a candidate of such front-loading. In fact, as far as I know, I’m the only one to note that the gene for the ribosomal protein s5 also seems to code for a protein that is expressed in the mammalian brain (see here and here).
A fresh new study has just been published that fits seamlessly with the above essays:
According to this site:
In three papers published back-to-back in Science, they provide the first comprehensive picture of a minimal cell, based on an extensive quantitative study of the biology of the bacterium that causes atypical pneumonia, Mycoplasma pneumoniae. The study uncovers fascinating novelties relevant to bacterial biology and shows that even the simplest of cells is more complex than expected.
A network of research groups at EMBL’s Structural and Computational Biology Unit and CRG’s EMBL-CRG Systems Biology Partnership Unit approached the bacterium at three different levels. One team of scientists described M. pneumoniae‘s transcriptome, identifying all the RNA molecules, or transcripts, produced from its DNA, under various environmental conditions. Another defined all the metabolic reactions that occurred in it, collectively known as its metabolome, under the same conditions. A third team identified every multi-protein complex the bacterium produced, thus characterising its proteome organisation.
“At all three levels, we found M. pneumoniae was more complex than we expected,” says Luis Serrano, co-initiator of the project at EMBL and now head of the Systems Biology Department at CRG.
So in what ways is this minimal cell more complex than expected?
To really appreciate the beauty of the SRP system, we should look more closely at the major players. But first, let’s make things more manageable. Lucky for us, the bacterium E. coli has a scaled-down version of the system that nevertheless functions much like the system seen in human cells . The RNA is much smaller, being only 114 nucleotides in length and thus lacking the Alu domain . Furthermore, instead of having six different proteins as part of the SRP, the E. coli version has only one, known as Ffh. Since there is only one, we’ll just call Ffh the ‘particle protein.’ E. coli also has the receptor (FtsY) and the translocon (SecY). Thus, the system is actually quite simple, being composed of a small RNA molecule (4.5S RNA) that is bound by the particle protein which in turn binds to the receptor and the translocon.
Let’s first put the particle protein under the microscope.
Let’s sketch out the basic events associated with getting a protein across the membrane. We’ll join the story after the gene for this protein has been expressed and an RNA molecule coding the amino acid sequence is synthesized. This RNA is known as messenger RNA (mRNA) and it is ultimately fed into the ribosome where its sequence of nucleotides will be decoded and used to string together a particular sequence of amino acids. (see animation here).
If we are about to explore the signal recognition particle through the telic lens, it might help some people to familiarize themselves with the molecular machine known as the ribosome. So sit back and enjoy the protein synthesis show.
Let me explain some more about the human brain protein that is encoded by the ribosomal S5 protein.
As most of you probably know, DNA is a double-stranded chain of nucleotides. When it is time to express a gene, the RNA polymerase unwinds the DNA and uses only one of the strands to make a copy in the RNA format as shown in the figure below:
What I showed with S5 is that while the bottom strand codes for this highly conserved ribosomal protein, the upper complementary strand, if it were to be transcribed and translated, would code for an unnamed protein product isolated from the human brain.
We have been focused on the ribosome as one plausible vehicle for front-loading evolution. This hypothesis led us to successfully expect ribosomal proteins would carry out additional functions and that some portions of the ribosomal RNA might actually code for protein. So it’s time to dig a little deeper.
I recently noted that the small ribosomal subunit protein, S5, also moonlights in the differentiation of red blood cells. One thing that is striking about S5 is its highly conserved amino acid sequence.