The so-called LINE-1 retrotransposon is a mobile genetic element that can multiply and insert itself into chromosomal DNA at many different locations. This disturbs the genetic code at the site of integration, which can have serious consequences for the organism. On the other hand, this leads to genetic variation, an absolute prerequisite for the evolution of species.
The structure of the L1ORF1p protein now allows a much more precise investigation of the mechanism of LINE-1 mobilization. This provides new insight into the relation between retrotransposons and retroviruses and probably also into certain evolutionary processes in humans and animals. Moreover, the researchers assume that the mechanism of LINE-1 retrotransposition can be exploited one day to precisely insert genetic information into specific locations. This would be an alternative to contemporary, less location-specific methods that are based on a retroviral mechanism. (PNAS, January 20th, 2009)
The LINE-1 retrotransposon is a mobile gene that has multiplied massively in the history of the human genome. Presently, approximately 17 per cent of our DNA consist of LINE-1 sequences. This is an enormous proportion if one considers that the roughly 30.000 human proteins are encoded by less that 5 per cen of the DNA. The LINE-1 retrotransposon not only propagates itself, but also is responsible for the genomic integration of approximately one million Alu-sequences (another parasitic gene). Alu-sequences are only present in higher primates and occupy another 10 per cent of our genome. The insertion of LINE-1 and Alu sequences is a continuous process and roughly every Elena Khazina and Oliver Weichenrieder / Max Planck Institute for Developmental Biologytwentieth newborn is estimated to contain at least one new insertion of such an element. Consequently, there rarely is a human gene that has not been affected in the past by the integration of a LINE-1 or Alu element. "It is difficult to believe that the massive integration of LINE-1 and Alu sequences remained without consequences on human evolution. Thus it is surprising how little we know so far about the mechanism of retrotransposition and about the proteins and nucleic acids involved in this process", says Oliver Weichenrieder, leading scientists at the Max Planck Institute for Developmental Biology. The researchers therefore try to gain new insights via the biochemical characterisation of the involved molecules and via the determination of their molecular structures. This provides the basis for a detailed functional analysis and reveals similarities to already known proteins, especially similarities that are not obvious from a simple comparison of the respective amino acid sequences.
In the presently published work Elena Khazina und Oliver Weichenrieder characterize one of two proteins that are encoded by the human LINE-1 retrotransposon. This so-called L1ORF1p protein binds to LINE-1 RNA, which was transcribed from a LINE-1 element in the genomic DNA. Subsequently, L1ORF1p likely supports the following reverse transcription of LINE-1 RNA into DNA. This process happens directly at the genomic integration site of the new LINE-1 element. The researchers show that the L1ORF1p protein consists of three parts. The first part causes a self-association such that always three molecules come together to form a trimer. The other two parts are necessary for binding LINE-1 RNA. "Especially surprising was the identification of a so-called RRM domain in the middle part of the protein, since this part was believed so far to be rather unstructured", says Elena Khazina. "Our crystal structure clearly proves the existence of this domain. Meanwhile we identified RRM-domains also in other retrotransposons, in a variety of animal and plant species", adds the structural biologist. RRM-domains (RNA Recognition Motif) occur frequently in the cell, particularly in RNA-binding proteins. The existence of an RRM-domain in L1ORF1p now explains why L1ORF1p binds LINE-1 RNA and how this could happen in detail. The insight into the structure of the L1ORF1p protein provides a new perspective and a good basis for future investigations of those cellular processes that are exploited by the LINE-1 element for its own propagation, and also for those mechanisms that are available to the cell to prevent the excessive propagation of retrotransposons.Original publication
The Max Planck Institute for Developmental Biology conducts basic research in the fields of biochemistry, genetics and evolutionary biology. It employs about 325 people and is located at the Max Planck Campus in Tübingen. The Max Planck Institute for Developmental Biology is one of 79 research institutes that the Max Planck Society for the Advancement of Science maintains in Germany.
Dr. Susanne Diederich | Max-Planck-Gesellschaft
Navigational view of the brain thanks to powerful X-rays
18.10.2017 | Georgia Institute of Technology
Separating methane and CO2 will become more efficient
18.10.2017 | KU Leuven
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
18.10.2017 | Materials Sciences
18.10.2017 | Physics and Astronomy
18.10.2017 | Physics and Astronomy