Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

RNA lariat may tie up loose ends to decades-old mystery of retrovirus life cycle

09.01.2004


Studies on common baker’s yeast have led to the discovery of what may be a long-sought mechanism in the life cycle of retroviruses, including the human immunodeficiency virus (HIV). Knowing the details of this step in the infection process could help pinpoint targets for new classes of drugs to fight HIV.



In the Jan. 9 issue of the journal Science, Thomas Menees and Zhi Cheng of the University of Missouri-Kansas City describe the formation of a lariat structure with the genetic material of retrovirus-like elements in baker’s yeast and subsequent cutting of the lariat by a yeast enzyme. The findings reported in Science and in the December 2003 Journal of Virology are the payoff of a three-year research gamble by Menees and two postdoctoral researchers pursuing host-cell factors in retroviral infections.

In addition to filling a gap in biologists’ understanding of how retroviruses replicate, it may turn out that similar lariat structures occur elsewhere in healthy cells and play previously unrecognized roles in cellular processes such as gene activation.


"The work of Menees and his collaborators fills a real void in our understanding of how retroviruses propagate and how genetic information is faithfully copied," said Patrick Dennis, program director for microbial genetics at the National Science Foundation (NSF), which supported the research. "The RNA lariat provides a plausible mechanism for a key step that has remained a mystery since the process of reverse transcription was first presented almost 35 years ago."

The 1975 Nobel Prize in Physiology or Medicine was awarded to David Baltimore and Howard Temin, in part, for describing how retroviruses replicate. The genomes of most organisms are encoded in DNA, which is transcribed into single- stranded ribonucleic acid (RNA) and then translated into proteins. The genome of a retrovirus, on the other hand, starts as RNA, which must first be converted into double-stranded DNA. Early in this process, the partially built DNA has to shift from one end of the RNA strand to the other end. Subsequent research confirmed that this so-called "template shift" does in fact occur, but the precise mechanism has never been identified.

"The structure of the lariat was very provocative," Menees said. "It is perfectly positioned to support template shifting. In addition, the lariat fits with data that were already out there and helps explain some other anomalous data on retroviral DNA."

While circumstantial evidence suggests the RNA lariat is the missing link, Menees is careful to point out that further work is needed to show that retroviruses actually use the same host-cell enzyme and the lariat structure to replicate.

He surmises that the lariat structure had escaped detection for so long because of its transient nature. As the RNA is being transcribed into DNA, another part of the viral machinery "chews up" and destroys the RNA.

Yeast cells are common laboratory models because they are structurally similar to human cells, and the harmless retrovirus-like elements in yeast serve as models for HIV and other retroviruses because all encode their genetic information in RNA and use the same process to replicate themselves. The main difference is that retroviruses eventually leave to infect other cells, while the yeast’s retrovirus-like elements remain in their host cell.

Only a few retroviruses are known to infect humans, but they include HIV-1, HIV-2, and forms of the human T-cell lymphotrophic virus (HTLV). Other retroviruses are known to cause cancer in animals.

"The new results provide remarkable new insights into the process of reverse transcription of virus-like RNA into DNA," said Stephen Goff, Higgins Professor of Biochemistry and Molecular Biophysics and Microbiology at Columbia University, who saw Menees present the lariat findings at a scientific meeting in May 2003. "The possibility that there are new players in the process of transposition is very exciting. If it is confirmed that the same enzyme is required for HIV-1 replication, there is little doubt that a new aspect of virus replication will be targeted for drug intervention."


NSF Program Officer: Patrick Dennis, 703-292-9061, pdennis@nsf.gov

Principal Investigator: Thomas Menees, 816-235-1849, meneest@umkc.edu

The National Science Foundation is an independent federal agency that supports fundamental research and education across all fields of science and engineering, with an annual budget of nearly $5.3 billion. National Science Foundation funds reach all 50 states through grants to nearly 2,000 universities and institutions. Each year, NSF receives about 30,000 competitive requests for funding, and makes about 10,000 new funding awards. The National Science Foundation also awards over $200 million in professional and service contracts yearly.

David Hart | NSF
Further information:
http://www.nsf.gov/

More articles from Health and Medicine:

nachricht New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

nachricht New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

New gene catalog of ocean microbiome reveals surprises

18.08.2017 | Life Sciences

Astrophysicists explain the mysterious behavior of cosmic rays

18.08.2017 | Physics and Astronomy

AI implications: Engineer's model lays groundwork for machine-learning device

18.08.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>