CM – Prions can channel the messages of the RNA

Click here to log in with

or

Forgot Password?

Learn more

November 15, 2021

by Mike Williams, Rice University

Prions mostly get bad press, but they can be the key to controlling protein synthesis in cells.

googletag.cmd.push (function () {googletag.display (‘div-gpt-ad-1449240174198-2’);});

Prions, proteins that can fold and aggregate incorrectly, have been linked to many neurodegenerative diseases. However, some prions are involved in long-term memory storage. New models from Rice University scientists describe how they can regulate the translation of RNA messages into new proteins by creating organized protein synthesis factories.

A study led by theoretical physicist Peter Wolynes and PhD student Xinyu Gu with the support of Rice alumnus Nicholas Schafer suggests that two prions, either in aggregate or condensate form, can activate or suppress the translation of actin proteins, as the case may be which direction they bind mRNA.

The lab modeled « protein assembly lines » focused on CPEB and Rim4, two examples of the 240 known prion-coding genes also known to be RNA in bind to eukaryotic cells.

CPEB and Rim4 represent a kind of yin and yang when it comes to translation, because they are directly opposite in their binding to mRNA. Their orientation influences how and whether ribosomes can be recycled during protein synthesis when the RNA is built up on the prion.

How CPEB controls the translation of RNA messages has been a mystery. It was known to suppress translation when it was a monomer, but once it aggregated it activated translation. Gu set about explaining how this could happen, which was more complicated than she expected.

« CPEB itself does the translation in a bidirectional way, » said Gu. « If it’s a prion, it will improve translation, and if it’s in a less ordered condensate, it will suppress translation. Our model suggests a physical hypothesis about how this happens. »

In short CPEB proteins aggregate into prions that bind the 3 ‘end (also known as 3 prime) of mRNA. Ribosomes, the molecular machines that decipher RNA to assemble proteins, easily find the other end (the « start codon ») and then work their way towards the « stop codon » attached to the prion. As soon as the ribosomes reach that 3 ‘end, they are released and start the cycle again at the outer 5’ end.

Rim4, on the other hand, goes the opposite way, since it binds to the 5 ‘terminus of the mRNA and thus covers it. Now it is more difficult for the floating ribosomes to find the start codon, which effectively suppresses translation and makes the prion of Rim4 less efficient.

Interestingly, CPEB can be used in its monomer form before aggregation or as part of a condensate (also known as « Membrane-less organelle ») channel mRNA translation in exactly the opposite way.

« Most people think of protein-RNA condensates as not polarized; they think they’re some kind of random collection of things that are just glued together, » Wolynes said. « However, our model suggests that condensate still has some kind of vector effect if it has a locally polarized structure. Understanding the internal structure of membraneless organelles therefore becomes a critical question. »

Wolynes and his group at the Rice Center for Theoretical Biological Physics (CTBP) have previously shown that there is a symbiotic relationship between CPEB prions and actin, the structural building block of the cytoskeleton that gives cells their overall shape and forms the backbone in the spiky dendrites of neurons. They theorized that actin filaments pull on CPEB fibers, “locking in” memories by marking specific dendrites.

The new work suggests that the « vectorial » nature of mRNA translation and the specific polarity of the CPEB aggregates may explain how these aggregates exert an essential regulatory function on the synthesis of actin and other synaptic proteins. The mechanism can also be used by other biological systems.

Wolynes said the details revealed in the study are only a very small part of the mechanism of memory formation, with the understanding that there is much more to be learned.

« Memory formation is a very big problem, the ultimate solution to which will fill many blackboards, » he said. « So far we’ve only filled one small corner of a single tablet and another little corner over there. The deciphering of these complicated processes inspires our work in many areas of theoretical biological physics. »

Use this form if you have identified a typographical error, inaccuracy, or if you would like to submit a change request to the contents of this page.
For general inquiries, please use our contact form.
For general feedback, use the public comments section below (please follow the guidelines).

Your feedback is important to us. Due to the high volume of messages, however, we cannot guarantee individual responses.

Your email address will only be used to let the recipient know who sent the email. Neither your address nor that of the recipient will be used for any other purpose.
The information you entered will appear in your email message and will not be stored in any form by Phys.org.

Receive weekly and / or daily updates in your inbox.
You can unsubscribe at any time and we will never pass your data on to third parties.

This website uses cookies to make navigation easier, to analyze your use of our services, to collect data for the personalization of advertisements and to provide third-party content.
By using our website, you confirm that you have read and understood our privacy policy
and terms of use.