The Lasker Award, which is regarded as the ‘Wind Vane’ of the Nobel Prize. Professor Joan Argetsinger Steitz from Yale University won the 2018 Lasker Award for his 40 years of leadership in the field of bio-medicine, especially in the field of RNA biology. In this post, we will summarize the recent achievements in the field of RNA molecular biology research.
. Nature: Measuring RNA velocity predicts the future state and ultimate fate of a single cell
The health function of a given organ or the dysfunction that causes the disease stems from the normal behavior or behavioral abnormalities of the individual cells that make up the organ.
Recent technological advances have enabled scientists to analyze the effects of cells one cell at a time, but these techniques only produce static snapshots of cell activity. To date, the behavior of capturing individual cells without cryopreservation applied to predict its future still is not being achieved.
In a new study, researchers from Harvard Medical School and Karolinska Institute of the United States successfully captured cellular decision-making as a dynamic process for the first time. In this process, the cell decides what to do and where to go. This method is a mathematical model that can be used to estimate RNA velocity, the rate at which RNA changes over time, which can be used as a predictor of cell fate on an hourly scale. The relevant research results were published online in the Journal of Nature.
. Nature: Significant progress in revealing hidden signals that regulate protein expression in RNA
Scientists have known clearly that RNA encodes instructions that express proteins. The building blocks that make up RNA -- bases A, U, C, and G -- form a blueprint for protein-making machinery in cells. In order to express a protein, binding this complex to one end of the RNA and then scanning along the RNA until it reaches the AUG codon, which is the signal that begins to translate the genetic code into a protein.
Figure 1. Ded1p binding sites on 18S RNA and mRNAs.
During the scanning of the first AUG codon in RNA, this protein-producing complex often encounters sites (such as AUA) that differ only a base from AUG. In some conditions, protein synthesis begins with these alternative starting sites. However, it has been a mystery how this protein-producing complex chooses which alternative site to use.
In a new study, researchers from Case Western Reserve University described how alternative protein initiation complexes can be applied to initiate protein synthesis. The results of the study were published in the journal of Nature.
. Nat Methods: Developed an efficient new fixed-point RNA editing method that can be applied to replace the CRISPR/Cas gene editing method
The development of the CRISPR/Cas gene editing tool marks a revolutionary advancement in targeting genetic information which offers plenty of opportunities for basic research and gene repair. However, it is still risky to change gene - any errors it causes will be permanently stored in the genome. Therefore, it is possible to bring problems to individuals receiving DNA changes and his/her offspring at a later time.
Professor Thorsten Stafforst and his team at the Interdisciplinary Biochemistry Institute at the University of Tübingen in Germany have developed a low-risk alternative after 7 years efforts, that is, targeting changes at the RNA level. This new approach utilizes a normal cellular process - the genetic information encoded in the DNA is transcribed to produce RNA, which is degraded when the RNA is no longer needed. If the RNA is altered, the initial genetic information will remain in the DNA. Now, in a new study, the Stafforst team can utilize this alternative to accurately and efficiently edit these RNA transcripts in cells. The relevant results of the study were published in the issue of Nature Methods.
Although this idea is still controversial, it has completely conquered the cell biology community. Over the past decade, scientists have observed that proteins and RNA molecules condense into droplets or membrane-free condensates in many cell types, from bacteria to humans. They also point out that the same protein that forms droplets in healthy cells can "Solidify" in diseases such as neurodegenerative diseases. However, there are still some questions not being answered, such as what makes some molecules in the same droplet come together and excludes other molecules.
. Nature: A major breakthrough that structurally reveals the transcription initiation mechanism of RNA polymerase III
The mechanism for reading and parsing DNA codes as needed is common to all animals and plants, however, it is usually being interrupted by cancer. In a new study, researchers from the British Cancer Institute used cryo-electron microscopy (Cryo-EM) to magnify and capture images of this reading mechanism with unprecedented detail. This discovery of how this molecular mechanism works may open up new avenues for developing new approaches to cancer treatment. The relevant research results were published online in the journal of Nature.
Figure 2. Proposed model in which RNA-RNA interactions derived from mRNA structure.
Specifically, these researchers capture the picture of a molecular machine called RNA polymerase III (PolIII) that binds to DNA, separating its two strands, and preparing a transcribed DNA code with exquisite and unprecedented detail. PolIII is critical for cells in all eukaryotes, including all animals and plants. In cancer, PolIII is more active, thereby causing cancer cells to produce a greater number of building blocks which is needed for their growth and proliferation, such as the amino acids that make up the protein. All of which is due to the rapid growth and split, that leads them to become extremely dependent on the components in the PolIII complex.
References
- MannoGL, et al. RNA velocity of single cells. Nature, 2018.
- Guenther U P, et al. The helicase Ded1p controls use of near-cognate translation initiation codons in 5′UTRs. Nature, 2018.
- Vogel P, et al.Efficient and precise editing of endogenous transcripts with SNAP-tagged ADARs. Nature Methods, 2018, 15(7):535.
- Langdon E M, et al.MRNA structure determines specificity of a polyQ-driven phase separation. Science, 2018:eaar7432.
- Abascal-Palacios G, et al. Structural basis of RNA polymerase III transcription initiation. Nature, 2018, 553(7688):301.