Biochemical controls: how RNA is supplied and delivered (Introduction)

by David Turell @, Monday, March 06, 2023, 19:09 (278 days ago) @ David Turell

Like American mail ZIP codes, there is a very definite system:

"RNA is a chemical cousin of DNA. It plays many roles in the cell, but perhaps it's most well-known as the relay messenger of genetic information. RNA takes a copy of the information in DNA from its storehouse in the nucleus to sites in the cell where this information is decoded to create the building blocks—proteins—that make cells what they are. This transport process is critical for animal development, and its dysfunction is linked to a variety of genetic diseases in people.

"In some ways, cells are like cities, with proteins carrying out specific functions in the "districts" they occupy. Having the right components at the right time and place is essential.


"The instructions for making a given protein are contained within RNA. One way to ensure proteins are where they are supposed to be is to transport their RNA blueprint to where their specific functions are needed. But how does RNA get where it needs to be?


"For a handful of mRNAs—or RNA sequences coding for specific proteins—researchers have an idea about how they're transported. They often contain a particular string of nucleotides, the chemical building blocks that make up RNA, that tell cells about their desired destination. These sequences of nucleotides, or what scientists refer to as RNA "ZIP codes," are recognized by proteins that act like mail carriers and deliver the RNAs to where they are supposed to go.


"We found that one protein that regulates neurite production, named Unkempt, repeatedly appeared with ZIP code-containing RNAs. When we depleted cells of Unkempt, the ZIP codes were no longer able to direct RNA transport to neurites, implicating Unkempt as the "mail carrier" that delivered these RNAs.

"With this work, we identified ZIP codes that sent RNAs to neurites (in our analogy, the bank). But where would an RNA containing one of these ZIP codes end up if it were in a cell that didn't have neurites (a city that didn't have a bank)?

"To answer this, we looked at where RNAs were in a completely different cell type, epithelial cells that line the body's organs. Interestingly, the same ZIP codes that sent RNAs to neurites sent them to the bottom of epithelial cells. This time we identified another mail carrier, a protein called LARP1, responsible for the transport of RNAs containing a particular ZIP code to both neurites and the bottom end of epithelial cells.

"How could one ZIP code and mail carrier transport an RNA to two different locations in two very different cells? It turns out that both of these cell types contain structures called microtubules that are oriented in a very particular way. Microtubules can be thought of as cellular streets that serve as tracks to transport a variety of cargo in the cell. Importantly, these microtubules are polarized, meaning they have ingrained "plus" and "minus" ends. Cargo can therefore be transported in specific directions by targeting to one of these ends.


"We could compare this process to a mailing address. While the top line ("The Bank") tells us the name of the building, it's really the address and street name ("150 Maple Street") that contains actionable information for the mail carrier. These RNA ZIP codes send RNAs to specific places along microtubule streets, not to specific structures in the cell. This allows for a more flexible yet uniform code, as not all cells share the same structures."

Comment: the bits and pieces of this complex system cannot be evolved bit by bit. It must be designed to all be together from the beginning.

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