Navigation Links
Structure of RNAi complex now crystal clear
Date:6/20/2012

CAMBRIDGE, Mass. (June 20, 2012) Researchers at the Whitehead Institute and Memorial Sloan-Kettering Cancer Center have defined and analyzed the crystal structure of a yeast Argonaute protein bound to RNA. This complex plays a key role in the RNA interference (RNAi) pathway that silences gene expression. Describing the molecular structure of a eukaryotic Argonaute protein has been a goal of the RNAi field for close to a decade.

"You can learn a lot from biochemical experiments, but to more fully understand a protein like Argonaute, it's useful to know where all of the atoms are and which amino acids are playing important roles," says Whitehead Institute Member David Bartel, who is also an MIT professor of biology and a Howard Hughes Medical Institute (HHMI) investigator. "Learning the Argonaute crystal structure is an important step in understanding the RNAi biochemical pathway and will be the basis for many future experiments."

The yeast Argonaute structure is described in the June 21st print issue of Nature.

In humans and most other eukaryotes, the RNAi pathway can reduce cellular protein production by reducing the proteins' RNA templates. By exploiting this pathway, scientists are able to knock down the expression of specific proteins and thereby determine their roles within the cell or organism. The RNAi pathway has also been of considerable interest for the treatment of human disease.

RNAi depends on two proteins, Dicer and Argonaute. Dicer recognizes double-stranded RNA (dsRNA), latches onto it, and chops it into pieces 21-23 nucleotides long. Argonaute recognizes the dsRNA bits, discards one strand, and uses the other as a guide. When a single-stranded RNA matches the guide RNA's sequence, Argonaute cleaves the targeted RNA, thereby preventing it from serving as a template for protein production.

To determine the structure of Argonaute, Bartel and graduate student David Weinberg partnered with Kotaro Nakanishi in Dinshaw Patel's lab at Sloan-Kettering. Although the team expected to solve the structure of Argonaute alone, they were surprised to find that the protein came along with small bits of RNA that were also observed in the structure. The incorporation of these RNAs had switched the protein into an activated state that contained a four-component active site, the identification of which solved a longstanding mystery of what constituted the "missing" fourth component. With the structure of this complex in hand, scientists now have a better understanding for how it works.

"Seeing the crystal structure of a eukaryotic Argonaute for the first time was very excitingit's such a large protein with a complicated topology and many moving parts," says Weinberg. "It's a really impressive molecular machine."


'/>"/>

Contact: Nicole Giese Rura
rura@wi.mit.edu
617-258-6851
Whitehead Institute for Biomedical Research
Source:Eurekalert

Related biology news :

1. Detector of DNA damage: Structure of a repair factor revealed
2. Study provides new insights into structure of heart muscle fibers
3. CSHL researchers solve structure of human protein critical for silencing genes
4. Psychiatric medication effects on brain structure
5. Mechanical properties and microstructure of cranial and beak bones of the woodpecker and the lark
6. Expedition to undersea mountain yields new information about sub-seafloor structure
7. Autism risk gene linked to differences in brain structure
8. Scientists produce eye structures from human blood-derived stem cells
9. Crystal structure of archael chromatin clarified in new study
10. Studies reveal structure of EV71, a virus causing childhood illnesses
11. A trained palate: Understanding complexities of taste, smell could lead to improved diet
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/28/2016)... , April 28, 2016 First quarter 2016: ... up 966% compared with the first quarter of 2015 ... SEK 589.1 M (loss: 18.8) and the operating margin was 40% ... 0.32) Cash flow from operations was SEK 249.9 M ... revenue guidance is unchanged, SEK 7,000-8,500 M. The operating ...
(Date:4/15/2016)... 2016  A new partnership announced today will ... decisions in a fraction of the time it ... high-value life insurance policies to consumers without requiring ... Force Diagnostics, rapid testing (A1C, Cotinine and HIV) ... pressure, weight, pulse, BMI, and activity data) available ...
(Date:3/31/2016)... March 31, 2016   ... or the "Company") LegacyXChange is excited to ... its soon to be launched online site for trading ... ) will also provide potential shareholders a sense ... technology to an industry that is notorious for fraud. ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... 2016 Epic Sciences unveiled a liquid ... to PARP inhibitors by targeting homologous recombination deficiency ... new test has already been incorporated into numerous ... types. Over 230 clinical trials are ... including PARP, ATM, ATR, DNA-PK and WEE-1. Drugs ...
(Date:6/24/2016)... ... , ... Researchers at the Universita Politecnica delle Marche in Ancona combed medical ... mesothelioma. Their findings are the subject of a new article on the Surviving Mesothelioma ... in the blood, lung fluid or tissue of mesothelioma patients that can help point ...
(Date:6/23/2016)... ... 2016 , ... UAS LifeSciences, one of the leading manufacturers ... Probiotics, into Target stores nationwide. The company, which has been manufacturing high quality ... list of well-respected retailers. This list includes such fine stores as Whole Foods, ...
(Date:6/23/2016)... /PRNewswire/ - FACIT has announced the creation of ... company, Propellon Therapeutics Inc. ("Propellon" or "the Company"), ... portfolio of first-in-class WDR5 inhibitors for the treatment ... represent an exciting class of therapies, possessing the ... cancer patients. Substantial advances have been achieved with ...
Breaking Biology Technology: