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The Explorer's Guide to Biology
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Drs. Fire and Mello's unexpected discovery of RNA interference (RNAi) that lead to their Nobel prize in Medicine and Physiology in 2006 revealing a natural mechanism cells use to control viral response, growth, and differentiation, and has ushered in a new era of RNAi-based treatments for diseases such as hereditary transthyretin-mediated amyloidosis (hATTR).
RNA interference (RNAi) is an important process, used by many different organisms to regulate the activity of genes. This animation explains how RNAi works and introduces the two main players: small interfering RNAs (siRNAs) and microRNAs (miRNAs). We take you on an audio-visual journey, diving into a cell to show how genes are transcribed to make messenger RNA (mRNA) and how RNAi can silence specific mRNAs to stop them from making proteins. The animation is based on the latest research, to give you an up-to-date view.
If you'd like to know more about the structures and processes you see in this video, check out the accompanying slideshow: http://www.nature.com/nrg/multimedia/...
Date: May 31, 2022Source: Cold Spring Harbor Laboratory
Summary: Cells rely on a process known as RNA interference (RNAi) to control protein production. The centerpiece of that process is the protein Argonaute, which seeks out and destroys mRNA molecules. Scientists have now discovered how Argonaute efficiently jumps from one target to the next. Their work may help improve current RNAi-based therapies and develop better ones in the future.
Cells rely on a process known as RNA interference (RNAi) to control protein production. The centerpiece of that process is the protein Argonaute, which seeks out and destroys mRNA molecules. Cold Spring Harbor Laboratory scientists discovered how Argonaute efficiently jumps from one target to the next. Their work may help improve current RNAi-based therapies and develop better ones in the future.
Cells produce proteins like little factories. But if they make too much at the wrong times it can lead to diseases like cancer, so they control production with a process called RNA interference (RNAi). As of July 2021, several drugs already take advantage of RNAi to treat painful kidney and liver diseases -- with another seven in clinical trials. There is a lot of potential for RNAi therapeutics, and Cold Spring Harbor Laboratory (CSHL) researchers are working hard to paint a complete picture of the process, to improve therapies today and make better ones tomorrow.
CSHL Professor & HHMI Investigator Leemor Joshua-Tor and recent CSHL School of Biological Sciences graduate Brianna Bibel are filling in some of the blanks. They recently discovered how RNAi's workhorse protein Argonaute (Ago) leverages limited resources to keep protein production on track.
It's important to understand exactly how RNAi works because it's such a basic and heavily used process, Joshua-Tor said. It also offers a kind of safety net for therapeutics because it doesn't make permanent changes to cells and can be reversed. Joshua-Tor says:
"For therapeutics, you'd kinda maybe not wanna mess around with the genome so much. In all these kinds of things, you wanna know exactly what's happening, and if something isn't working, then you know what to do and where to look. The more information you have, the better it is -- you get a complete picture of what's happening."
Ago helps cut off protein production by finding, binding, and destroying molecules called mRNA -- which tell cells to make proteins. But the amount of Ago in the body pales in comparison to the amount of mRNA it must target. After destroying one, the protein is still capable of finding another but it can't move on without help. Bibel discovered how cells use a process called phosphorylation to break Ago's grip on a mRNA target, allowing it to commute to the next. Bibel explains:
"Our theory is that having phosphorylation promote release is a way that you could free up Argonaute because when the target gets released, the guide's still there and it's super duper stable. So our thinking is that by phosphorylating it, you're going to free it to go repress other targets -- because it's still totally capable of doing that work."
Bibel hopes her discovery will come in handy as research into RNAi continues. "A lot of great advances in science come from just doing basic research," she said. "And this is one of those basic research questions, trying to figure out how this is working."
Story Source:
Materials provided by Cold Spring Harbor Laboratory. Original written by Nick Wurm. Note: Content may be edited for style and length.
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