Co-evolution between a "parasite gene" and its host



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Figure: Søren Lykke-Andersen.
<b>Figure 1 | The structure of the snoRNA dictates the production of the protein-coding host. </b> Schematic illustration of how two different snoRNA structures impact the expression of the host gene. Left: specific snoRNA structure obtained when snoRNA proteins bind to the snoRNA. This structure facilitates an alternative splicing of the RNA, inhibiting the production of protein. Right: Alternative snoRNA structure formed by the naked snoRNA, which leads to the production of a protein-coding mRNA, ultimately producing protein. Figure: Søren Lykke-Andersen.
<b>Figure 2| Evolution of snoRNA genes and function.</b> Left: Independent snoRNA gene unit, which is the predominant snoRNA gene organization in e.g. yeast. Middle: snoRNA hosted in the intron (red line) of a protein-coding gene. The green boxes indicate coding regions called exons. This is the predominant snoRNA gene organization in e.g. humans. Right: In the described study it was demonstrated that a specific intron-hosted snoRNA controls the splicing of its host transcript. Figure: Søren Lykke-Andersen.

2018.09.19 | Research

Co-evolution between a "parasite gene" and its host

A Danish research team has delineated a complex symbiosis between a ‘parasitic’ noncoding RNA gene and its protein coding ‘host’ gene in human cells. The study reveals how co-evolution of the host gene and parasite gene has shaped a feedback mechanism in which the parasite gene plays a completely new and surprising part as regulator of the host…

Advanced fluorescence microscopy has shown that the structural change on the ribosome of the protein called EF-Tu is far smaller than previously assumed. Photo: Yale E. Goldman.
Decoding the genetic code on the ribosome. The figure shows how aa-tRNA (bend red line) is delivered by EF-Tu (green) onto the ribosome (light blue) in a step-by-step process that can be followed by advanced fluorescence microscopy. In step I, aa-tRNA is bound in complex with EF-Tu·GTP near the ribosomal A-site. In step II, the first test is performed to see whether codon and anticodon match, which can lead to the hydrolysis of GTP bound by EF-Tu. After a further proofreading of aa-tRNA anticodon in step III, the aa-tRNA is fully accommodated in the ribosomal A-site with the help of EF-Tu, which begins to change shape during this step. EF-Tu completes its structural change only after leaving the ribosome in Step IV. Figure: Chunlai Chen and Charlotte Rohde Knudsen.

2018.09.17 | Research

Advanced fluorescence microscopy reveals new aspects of protein pathways on the ribosome

The protein called translation elongation factor EF-Tu is a well-known player in the protein synthesis process. A new scientific article describes novel aspects of this well-described protein, which appears to play an even more important role in securing the accuracy of translation than previously assumed. The results may have an influence on the…

Researchers from Aarhus University have completed a new successful screening strategy where they have identified novel inhibitors of αlpha-synuclein aggregation. This may help develop a cure for Parkinson's disease. (Image: Colourbox.com)
Graphical overview of a screening of 746,000 compounds for inhibitory effects of alpha-synuclein aggregation. (Graphics: Professor Daniel Otzen)

2018.09.11 | Research, Knowledge exchange

New high-throughput screening study may pave the way for future Parkinson’s disease therapy

Parkinson's disease is the most common neurodegenerative disease; currently there is no cure. Aggregation of the protein α-synuclein plays a key role in this disease. Together with a US drug company, AU researchers have now carried out a new screening strategy which has identified novel and structurally diverse aggregation inhibitors.

<b>GTPases are molecular switches that follow a characteristic cyclic pattern.</b> When a GTPase is bound to GTP (right), it is active or "on". In this state, the GTPase can bind to so-called effector molecules (below), which transmit the GTPase’s signal further within the cell. The interaction with the effector causes the GTPase to hydrolyse the bound GTP, thereby rendering the GTPase to its inactive "off" GDP-bound form (left). The GTPase can be reactivated via interaction with a guanine-nucleotide exchange factor that promotes the replacement of the bound GDP with GTP (top). Figure: Charlotte Rohde Knudsen.
<b>Measurement of distances in EF-Tu's structural extremes.</b> Elongation factor Tu consists of three structural units, of which domain I (green) is involved in the binding of GTP/GDP (magenta). Domain I can rotate relative to Domain II/III (light/dark blue), thus creating two structural extremes: a "closed" active state (left) and an "open" inactive state (right). The distance between the fluorescence donor and acceptor in the two forms is shown by the yellow line. So far, it has been assumed that the closed state occurred upon binding of GTP, but the new results show that EF-Tu·GTP must bind to aminoacylated tRNA and the ribosome before the active state is formed. Figure: Charlotte Rohde Knudsen.

2018.09.10 | Research

Molecular switches are not just "on" or "off"

It is not always easy to see if a switch is on or off! A new study shows that the same can be true of a molecular switch. This knowledge gives a new insight into the molecular switches, the GTPases, many of which have medical potential.