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
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy