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
05/01/2027
Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be ...
04/08/2026
Dalet, a leading technology and service provider for media-rich organizations, t...
04/07/2026
April 7 2026, 19:00 (PDT) Detective Conan: Fallen Angel of the Highway Opens in...
01/06/2026
January 6 2026, 05:30 (PST) Dolby Sets the New Standard for Premium Entertainment at CES 2026
Throughout the week, Dolby brings to life the latest innovatio...
06/05/2026
Polands Miecznik-class frigates are part of the largest contract in Polish shipbuilding history. (Image Credit: PGZ Stocznia Wojenna)...
06/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
06/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
06/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
06/05/2026
Riedel Communications today announced the expansion of its leadership structure as part of a strategic initiative to strengthen both its operational management ...
06/05/2026
For nearly three decades, Veteran Production Sound Mixer and Five-time Emmy Award Winner Dirk Sciarrotta has helped define the sonic identity of the long-runnin...
06/05/2026
ZEISS CinCraft LensCore: Cinema Lens Looks for Compositing
Brie Clayton May 6, 2026
0 Comments
ZEISS announces the launch of CinCraft LensCore, a nove...
06/05/2026
Wisycom Solves Extreme RF Challenges Across Miles of Live Action for Gravity Med...
06/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
06/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
06/05/2026
Narrative Entertainment has partnered with Encompass to deliver high-quality subtitling of its Great! network content using the Altitude Intelligence AI assiste...
06/05/2026
SipRadius, widely recognized for making content processing and connectivity secure and seamless, is proud to launch a dramatic new approach to AI content creati...
06/05/2026
When the broadband and media industry gathers at ANGA COM in Cologne from May 19 to 21, Big Blue Marble will be at the forefront. The international broadcast an...
06/05/2026
Cinegy GmbH, a leading developer of software-defined television technology, is proud to exhibit at MPTS for the first time. Visitors to the stand will discover ...
06/05/2026
Val Jeanty Receives 2026 Doris Duke Artist Award Jeanty, a composer, percussionist, and turntablist, is the fourth Berklee recipient of the prestigious award ...
06/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
06/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
06/05/2026
When live cycling races and international marathons stretch for miles across cities and countryside, there is no margin for RF failure in live broadcast. As Chi...
06/05/2026
Oberkochen/Germany, May 5, 2026
ZEISS announces the launch of CinCraft LensCore, a novel solution for creating physically based cinematic lens looks for visual...
06/05/2026
Wuppertal May 6, 2026
Riedel Expands Leadership Structure, Appoints Marc Engro...
06/05/2026
SAN JOSE, Calif. - May 6, 2026 - Harmonic (NASDAQ: HLIT) today announced its latest broadband innovations for ANGA COM 2026, highlighting its vision for a new e...
06/05/2026
Statement from Rupert Murdoch, Chairman Emeritus, Fox Corporation on Ted Turner&...
06/05/2026
Friday 8 May on RT One and RT Player
Meet the NSPCA team caring for and protecting animals in need in this six-part series
Fly on the wall, six-part series...
06/05/2026
The race to build the world's most powerful AI factories demands networking ...
06/05/2026
How changes to proteins can alter drug interactions for new precision therapies Scripps Research team maps how chemical modifications to proteins affect drug bi...
05/05/2026
Experts from the world of academia, tech, business, politics and media convened for a Thomson Talks at the Cambridge Disinformation Summit in April. It's th...
05/05/2026
Three phones were hardwired for power and transmission to the truck; camera feat...
05/05/2026
The creative studio behind campaigns for the NBA, Fanatics Sportsbook & Casino, ...
05/05/2026
Nielsen has announced results from a co-viewing pilot program covering February&...
05/05/2026
viztrick AiDi, an on-device AI solution developed by Nippon TV, delivered global...
05/05/2026
ARRI has announced Omnibar, a battery-powered, IP65-rated multi-color LED linear...
05/05/2026
Imagine Communications has announced that France T l visions is the first broadc...
05/05/2026
The Women's National Basketball Association (WNBA) and Bell Media today announced a multiyear agreement to broadcast and stream WNBA games in Canada beginni...
05/05/2026
SVG is proud to announce Warner Bros. Discovery's Techwood Studios in Atlant...
05/05/2026
With no operator required, AutoMic workflow automates talent identification on U...
05/05/2026
A crash in 2015 set the industry back, but this winter proved that drones are he...
05/05/2026
Another year, and more proof that Asia continues to shape some of the world's most exciting new sounds. This year's RADAR artists draw from deep local r...
05/05/2026
The Austin City Limits Music Fest 2026 lineup just dropped, and this year, Spoti...
05/05/2026
New drum machine book campaign incoming
Bjooks have announced that during Superbooth 2026, they will be launching a Kickstarter campaign to fund the product...
05/05/2026
Flagship all-in-one production bundle updated
The latest version of Native Instruments' flagship virtual instrument and plug-in bundle has just been ann...
05/05/2026
Rohde & Schwarz to host RF Testing Innovations Forum 2026, helping design engine...
05/05/2026
L3Harris provides communications, electronic warfare, sensors and mission systems that enable Virginia-class submarine crews to operate with confidence in conte...
05/05/2026
The company grew by 7.6% in net revenue and 16.3% in EBITDA, achieving a 33% inc...
05/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
05/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
Scripps Research Institute Scientists Capture Picture of MicroRNA In Action The Findings Will Help Guide Drug Design 
