Learning Update — July 6, 2021
mRNA caps. Horses, wooden pipelines, iron railroads, and wholesale transfer pricing power.
mRNA Caps
I have partly answered the question I had: why is one G nucleotide on the mRNA cap sufficient to protect the cap end (while the tail needs 100-200 A’s)?
The answer is that, it’s not! There’s a lot going on. The cap of an mRNA is not “just” a G nucleotide — that’s just a simplification.
Here’s a G:
An mRNA cap is actually a modified G, with a bunch of stuff attached to it.
There are four (known?) mRNA caps:
Highlighted in green, Cap 0 has an OH whereas Cap 1 has an OMe and Cap 2 has an additional OMe. You can see that the G molecule starts each cap (on the left side, “upside down”).
In fact, TriLink BioTechnologies (part of Maravai LifeSciences) has developed an mRNA 5’ cap that does not have to start with G. (Maravai’s 5’ caps have been used in the mRNA vaccines of both BioNTech and Moderna.)
The four (known?) types of mRNA caps are:1
Cap 0:
Has no methyl groups (CH₃ or Me) attached. Only a hydrogen (H).
An intermediate in the structure of a cap, but not found in mature eukaryotic (animals, plants, fungus) mRNA messages.
Cap 1:
Has a methyl group (CH₃ or Me) where Cap 0 has a hydrogen (H).
Found in all eukaryotic (animals, plants, fungus) mRNA.
Cap 2:
Has an extra methyl group (CH₃ or Me) attached.
Found in ~50% of eukaryotic mRNA
We don’t know much about Cap 2’s because it has only recently been possible to easily generate them in the lab and experiment with.
m6Am Cap:
I don’t know much else about this one except the name.
There is “recent evidence” that this cap is found in ~30% of eukaryotic mRNA caps, and that it regulates “translational initiation” and mRNA stability.
Interestingly, many viruses have a Cap 1 structure and will even “steal” methyl groups from the caps of target eukaryotic cells they are infecting and attach it to their own RNA to achieve Cap 1 status.
This is evidence that the caps are doing something important and that Cap 1 is preferred to Cap 0, at least sometimes.
Horses, Wooden Pipelines, Iron Railroads, and Wholesale Transfer Pricing Power
The first oil pipeline (Tidewater) was made of wood, started around 1863ish (?), and was developed to:
1) get around the “teamster monopoly” — the use of wagons and horses — on shipping oil from Pennsylvania’s Oil Region to the Reading Railroad;
2) bypass Standard Oil’s monopoly on purchasing oil from producers (i.e. monopsony).
From The Prize:
From the first discoveries [of oil], teamsters, lashing their horses, had clogged the roads of the Oil Regions with their loads of barrels. They were more than just a physical bottleneck. Holding a monopoly position, they charged exorbitant rates; it cost more to move a barrel over a few miles of muddy road to a railway stop than to transport it by rail from western Pennsylvania all the way to New York. The teamsters’ stranglehold on transportation led to an ingenious effort to develop an alternative—transportation by pipeline. Between 1863 and 1865, despite much scoffing and public ridicule, wooden pipelines proved that they could carry oil much more efficiently and cheaply. The teamsters, seeing their position challenged, responded with threats, armed attacks, arson, and sabotage. But it was too late. By 1866, pipelines were hooked up to most of the wells in the Oil Regions, feeding into a larger pipeline gathering system that connected with the railroads.
Also:
Its construction was carried out with both deception and dispatch. Fake surveys were even taken to throw Standard off as to its route. Many doubted right up to the last moment that the pipeline would work. Yet, by May of 1879, oil was flowing in the pipeline.
Kids, always remember: If you have only one supplier of a necessary input, that supplier controls your profits. And on the demand side, if you have only one potential customer that you can sell to, that customer controls your profits.
These are the only two maps I could find of the first Tidewater Pipeline, and I’m not sure how accurate they are.
