Scripps Research Institute Scientists Capture Picture of MicroRNA In Action The Findings Will Help Guide Drug Design
LA JOLLA, CA October 30, 2014 Biologists at The Scripps Research Institute (TSRI) have described the atomic-level workings of microRNA molecules, which control the expression of genes in all animals and plants.
The findings add greatly to the understanding of a fundamental system of regulation in biology, and should accelerate the development of therapies that harness its power.
We've obtained the clearest picture to date of how these crucial gene regulators work, said TSRI Associate Professor Ian J. MacRae, who was senior investigator for the study reported in the October 31, 2014 issue of the journal Science.
The Gene Silencers
MicroRNAs, as their name suggests, are snippets of ribonucleic acid, only about 22 nucleotides long. Encoded by genes, they are meant to function as RNA molecules, and are never translated into proteins. In humans there are almost 2,000 distinct microRNAs, which collectively regulate somewhere between 30 and 80 percent of human genes.
MicroRNAs do their work by intercepting and effectively silencing the RNA transcripts of genes. These tiny gene-regulators operate in all multicellular organisms, including all plants and animals; even some viruses have them. Moreover, their normal workings appear to be disrupted in many human diseases. Yet their central importance in biology has become apparent only in the last decade or so, and the details of how they silence their targets have started to come into focus only in the last few years.
MicroRNAs operate not on their own, but in the company of large proteins called Argonautes, which microRNAs effectively guide to their RNA targets. In a study reported in Science in 2012, MacRae and his graduate student Nicole T. Schirle used X-ray crystallography techniques to determine, for the first time, the atomic structure of human Argonaute bound to a microRNA and its RNA target.
Seeing How the Process Works
In the new study, the researchers were able to determine the structure of human Argonaute-plus-microRNA in the act of binding to an RNA target. We could see from these structural data the details of how the process works, said MacRae.
The data show that Argonaute holds a microRNA molecule in a way that initially exposes only a few of its nucleotides presumably to minimize interactions with RNAs that aren't in its target set. These few exposed microRNA nucleotides will, however, stick to the complementary nucleotide sequences found on target RNAs. When such contact is made, Argonaute rearranges its structure to facilitate a tighter embrace of more closely matching targets.
A key helix structure on Argonaute moves out of the way, allowing further base-pairing between the microRNA guide and its target, said Schirle. In general, Argonaute changes its conformation so as to expand the binding and stabilize the interaction with an appropriate target RNA.
MicroRNAs bind to RNA targets that match its sequence only very partially, in short stretches, which is why a single microRNA may be able to intercept the transcripts of hundreds of different genes. When it binds such transcripts, the microRNA-Argonaute team summons other molecules that effectively block the transcripts from further meaningful activity. By contrast, related regulatory molecules called short interfering RNAs (siRNAs) match their RNA targets more completely, and induce Argonaute to silence those targets more directly, with a built-in enzyme that slices them in two.
The study hints at how Argonaute switches to this more direct mode of silencing. Slicing requires a catalytic magnesium ion, which has to be held in a precise position over the target, said Schirle. What we see now is that this magnesium ion is positioned in the wrong place in the Argonaute structure when a microRNA is bound to its target, so that the target won't be sliced. We propose that a more extensive pairing with the target RNA, as siRNAs make, would then swing the magnesium ion into the correct position to enable slicing.
Untapped Medical Potential
The new wealth of structural detail on microRNA-Argonaute function will be of broad scientific interest, but should also make a big impact on medicine. The great therapeutic potential of drugs that mimic or inhibit microRNAs to control key processes in cells is at this point completely untapped.
There is a whole new class of microRNA-targeting drugs that have been proposed and have started to be developed, said MacRae, and here we've provided information that should be very helpful in designing such drugs.
The paper, Structural basis for microRNA targeting, was also co-authored by Jessica Sheu-Gruttadauria, a graduate student in the MacRae Laboratory. Funding for the research was provided by the National Institutes of Health (R01 GM104475).
About The Scripps Research Institute
The Scripps Research Institute (TSRI) is one of the worlds largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists including two Nobel laureates work toward their next discoveries. The institutes graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.
# # #
For information:
Office of Communications
Tel: 858-784-26
Most recent headlines
06/10/2025
France T l visions, France's leading broadcaster, has received the 2025 EBU ...
04/09/2025
Monumental Sports & Entertainment (MSE), in collaboration with Dalet, has been a...
30/08/2025
WASHINGTON The Federal Communications Commission has adopted its FY 2025 Regulatory Fees Order that establishes the regulatory fee rates for the broadcast stati...
29/08/2025
Australian Red Cross and SBS launch training to help workplaces in the fight aga...
29/08/2025
The National Film and Video Foundation (NFVF), an agency of the Department of Sp...
29/08/2025
L3Harris Technologies has concentrated decades of expertise across the entire enterprise to develop affordable and reliable best-of-breed solutions to rapidly c...
29/08/2025
BURBANK, Calif. The CW Network and the Pac-12 Conference have announced a new media rights deal that will extend their broadcast partnership beginning with the ...
29/08/2025
NEW YORK Gracenote has released a new analysis of its global video dataset showing that the number of FAST channels grew nearly 14% from Q1 2025 and 76% since 2...
29/08/2025
SAN JOSE, Calif. Harmonic has announced a series of improvements to its live sports streaming solution that the company said will improve fan engagement, protec...
29/08/2025
NEW YORK and LOS ANGELES Fox Corp. and YouTube TV last night announced a renewal of the full portfolio of Fox networks, including Fox News Channel, Fox Business...
29/08/2025
Budapest, Hungary, August 2025 - The integration of Microsoft Teams Rooms (MTR) with Lightware's Taurus universal matrix switchers delivers a new level of f...
29/08/2025
Frequency, the engine behind many of the world's best-known streaming television channels, today announced it will launch Studio Live, a next-generation uni...
29/08/2025
In an era when AI and cyber resilience are essential, Scality will mark the 10th anniversary of Scality Day on October 16, 2025 in Paris. This flagship global e...
29/08/2025
Disguise's In-House Creative and Technical Teams Pre-Visualised, Programmed and Delivered Content for the Experience, All Powered by EX 3+
Technology solu...
29/08/2025
Disguise will be demonstrating the latest workflows for TV, film and live events on a number of partner booths at the show
Disguise, the industry-leading tech...
29/08/2025
STOCKHOLM, Sweden Accedo will showcase Accedo Compose, its AI agent-powered modular orchestration layer that assists streaming providers in transitioning client...
29/08/2025
LOS ANGELES Cineverse has announced that it is working with Xperi to bring four of its streaming channels to automobiles for the first time as part of the DTS A...
29/08/2025
DALLAS & ATLANTA Gray Media has announced an agreement with the sports streaming service Victory+ to simulcast 17 Dallas Stars NHL games in 15 television market...
29/08/2025
NEW YORK AND CULVER CITY Comcast NBCUniversal and Amazon have announced new and extended distribution agreements that will expand the content available on their...
29/08/2025
FOOTHILL RANCH, Calif. RED Digital Cinema will feature its Cine-Broadcast Module supporting live broadcast workflows during IBC2025, Sept. 12-15, at the RAI Ams...
29/08/2025
29 Aug 2025
Kyivstar Rings Opening Bell at Nasdaq Marking Landmark Listing and ...
29/08/2025
More than half of all NFL games live on Sky for the first timeFriday 29 August 2025
Sky Sports has announced a new three-year deal with the NFL, extending its ...
29/08/2025
Back to All News
RIV4LRIES: The Trailer of the New Series With Samuele Carrino ...
29/08/2025
Get ready for an inspiring and emotional insight into the world of competitive Irish dancing with My Story: Tomi Champion of the World airing on RT 2 this monda...
29/08/2025
RT has today announced that David McCullagh is to be the new presenter of RT Radio 1's flagship Today programme, which airs every weekday at 10am, replaci...
28/08/2025
By Kristin Feeley, Director, Documentary Film & Artist Programs
If you want to tell untold stories, if you want to give voice to the voiceless, you've got ...
28/08/2025
Directed by Steven Bognar and Julia Reichert, Sundance Institute-supported Amer...
28/08/2025
Corridos have been a cornerstone of M sica Mexicana for generations, telling stories rooted in everyday life. Now, a new chapter is taking shape: motivational c...
28/08/2025
Los corridos han sido un pilar de la M sica Mexicana durante generaciones, contando historias enraizadas en la vida cotidiana. Ahora, un nuevo cap tulo est tom...
28/08/2025
Earlier this month, we promised our Verano Forever party would bring the heat, a...
28/08/2025
L3Harris will provide the Polish F-16V fleet with the Viper Shield electronic warfare system as part of an upgrade program....
28/08/2025
Bilbao, August 26, 2025 - AgileTV, an international television and video technol...
28/08/2025
Ken Wilkinson is an Emmy Awards nominated New York audio engineer who specialises in production sound mixing for film, commercial, episodic and documentary work...
28/08/2025
NEW YORK FuboTV today announced that it will launch Fubo Sports, a skinny bundle that focuses on sports with a subscription price of $56 monthly....
28/08/2025
NEVADA City, Calif. At IBC2025, Sept. 12-15 at the RAI Amsterdam, Telestream will debut its new Global Ingest strategy, introducing a next-generation ingest arc...
28/08/2025
Dr. Rhoda Bernard Releases Groundbreaking Debut Book on Accessible Arts Educatio...
28/08/2025
TAG Video Systems, the leader in software-based IP end-to-end workflow monitoring, deep probing, and real-time visualization, has named Oliver Gappa as Sales Di...
28/08/2025
AI-based voice enhancement will be among a series of innovations making their IBC 2025 debut on the DHD stand B46 in Hall 8 at the RAI Amsterdam Convention Cent...
28/08/2025
Telef nica Servicios Audiovisuales (TSA), the leading system integrator and service provider in the media sector in Spain, with the support of Appear, the globa...
28/08/2025
To fully immerse sailing fans in the world's biggest offshore yacht race, production company, Optical Media turned to LiveU's On-site Production solutio...
28/08/2025
Working with Calrec on its most recent overhaul, radio and television broadcaster, WNED has migrated to a fully IP infrastructure with multiple Type R consoles,...
28/08/2025
Cleeng, the Subscriber Retention Management (SRM ) inventor, has unveiled Cleeng Pro, the first-ever direct-to-consumer (D2C) subscription management platform t...
28/08/2025
Zixi, the industry leader in live broadcast-quality video over IP, today announced that French media distribution platform OKAST has selected Zixi to enable rel...
28/08/2025
Solution offers a streamlined, speaker-free architecture to optimize integration with premium external loudspeakers and advanced loudness metering
Nixer Pro Au...
28/08/2025
Cinegy, the premier provider of software-defined television technology, has announced a strategic partnership with Vision One Touch Film Production Services L.L...
28/08/2025
Telestream, a global leader in media workflow technologies, will debut its new Global Ingest strategy at IBC2025, introducing a next-generation ingest architect...
28/08/2025
Tier 1 operator selects Broadpeak to power high-performance, unified CDN solution across Norway, Sweden and Finland
Broadpeak, a leader in streaming and moneti...
28/08/2025
Leading video software provider, Synamedia, today announced that 24 Frames Digital, one of India's leading live event streaming service providers, has chose...
28/08/2025
Meet VisualOn at IBC2025: See What's Next in AI-Powered Video Streaming Join VisualOn at IBC2025 and discover how our AI-driven Optimizer and advanced media...
Scripps Research Institute Scientists Capture Picture of MicroRNA In Action The Findings Will Help Guide Drug Design 
