Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cracking the Genomic Code: Gene Decoding Revealed at Atomic Level

06.12.2004


The critical decoding structure produced when modified nucleosides enable tRNA to decode by wobble recognition. Only the decoding region of a 50,000+ atom structure of the ribosome (small subunit) is shown. The modified nucleoside platform (orange) that stabilizes the codon-anticodon interaction, and the modified nucleoside that wobbles (green) are shown. The structure was determined at the atomic resolution of -3 angstroms (3 X 10 –10 meters).


A recent finding by a North Carolina State University biochemist advances the fundamental biology of how genetic information, encoded in DNA, is decoded for the production of proteins.

Dr. Paul F. Agris, professor of biochemistry at NC State, and academic colleagues from England and Poland show concrete evidence in favor of the 1966 “Wobble Hypothesis” offered by Francis Crick, the co-founder of the DNA molecule and its double-helix structure, and Agris’ own “Modified Wobble Hypothesis” posed in 1991. The scientists used x-ray crystallography of the cell’s protein-manufacturing unit, the ribosome, to provide a visual snapshot of the decoding process.

The research is published in the December 2004 edition of Nature Structural and Molecular Biology.



The Wobble Hypothesis was Crick’s attempt to make sense of how the cell decodes the genetic information of DNA – the molecule that constitutes all the genetic information in a cell – and then, from that information, makes biologically active proteins, Agris said.

DNA has 61 three-letter codes that are translated by transfer RNA (tRNA) into amino acids; proteins are made of amino acids. But there are only 20 natural amino acids. Squaring the disparity between the number of codes and the number of amino acids – there are three times as many codes as there are amino acids – became a hurdle for Crick and other early geneticists, Agris explained. Crick attempted to clear this hurdle with the Wobble Hypothesis. He based this theory on the first report of a tRNA molecule’s chemical structure discovered by Robert Holley in 1963.

Normally, RNA molecules are composed of four nucleosides: adenosine, guanosine, cytosine and uridine (A,G,C,U). But the tRNA molecule Holley studied included a modified nucleoside called inosine (I), Agris says. Seeing this inosine in an important area of the tRNA molecule – an area that read the three-letter DNA codes when the cell synthesizes proteins – led Crick to believe that a single tRNA used inosine to read more than one code, and that therefore the 61 codes were decoded by fewer than 61 tRNAs.

As an example, Agris used the amino acid alanine, which has four codes. Crick’s hypothesis would allow that only two tRNA molecules could be capable to decode all four alanine codes. Using the modified nucleoside I in place of A, G, C or U, one tRNA may be able to read three codes, effectively “wobbling” the reading. Twenty-five years after the Wobble Hypothesis, Agris proposed his Modified Wobble Hypothesis. It stated that modified nucleosides other than inosine would in some cases expand tRNAs ability to translate codes by wobbling to greater numbers of three-letter codes, whereas other modified nucleosides would restrict wobble to only one or two codes.

Now, in the recent paper, Agris and colleagues prove Agris’ alteration to Crick’s hypothesis was correct: Cellular modification of tRNA alters chemistry and structure in a manner critical for tRNA to decode more than one three-letter code. Using atomic-level resolution – in which researchers can distinguish atom from atom – and working with a tRNA specific for the amino acid lysine, Agris and his colleagues show modified nucleosides enabling tRNA to decode genomic information on the ribosome, the cell’s protein synthesis machinery.

Specifically, it shows modifications enabling the decoding of two codes. One modification acts like a platform on which decoding takes place, and the other allows a novel chemical and physical interaction to occur between tRNA and the code, Agris said. “This is the first visualization that modifications are critical for decoding the genome through wobble,” he said.

Agris says that 15 to 20 percent of tRNAs in all organisms require modified chemistries in order for codes to be properly read and protein synthesis to be successful. “An understanding of how modified nucleosides enable and improve wobble recognition of the three-letter codes for protein synthesis opens the possibility of using modified nucleosides to expand the cells’ use of tRNA to make new proteins, or in new ways to target the protein synthesis machinery in pathogens,” Agris said.

Mick Kulikowski | EurekAlert!
Further information:
http://www.ncsu.edu

More articles from Life Sciences:

nachricht Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Engineers program tiny robots to move, think like insects

15.12.2017 | Power and Electrical Engineering

One in 5 materials chemistry papers may be wrong, study suggests

15.12.2017 | Materials Sciences

New antbird species discovered in Peru by LSU ornithologists

15.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>