Shocked genetic RNA

Release date: 2013-03-07

Scientists see the latest in the scorpion filled with quirky RNA: naturally occurring circular RNA molecules affect gene expression. In the latest issue (February 27), Nature, two important research papers revealed that some circular RNA acts as a molecular "sponge" that binds and blocks tiny gene regulators called microRNAs. In addition, the researchers speculate that circular RNAs have many other functions. Nikolaus Rajewsky, a systemic biologist at the Max Delbrück Center for Molecular Medicine in Germany, said that these molecules constitute a "hidden unknown RNAs parallel universe." This discovery once again reminds people that RNA is not just an ordinary messenger between DNA and encoded proteins. In the past 20 years, researchers have discovered a large amount of unconventional RNA. Some lengths are unexpectedly short, others are surprisingly long, while others subvert the conventional function of preventing the translation of other RNA chains to form proteins. Almost all RNA is linear, and a small number of descriptions of circular RNAs in plants and animals have also been ignored as genetic accidents or experimental human factors. In fact, the advantages of linear RNAs may have been illusory. Classical RNA sequencing methods can only isolate those molecules that have the characteristic molecule "tail". The ends of circular RNAs are linked together and lack these tails and are therefore generally ignored. However, with advances in sequencing technology, biologists have accumulated a large collection of RNA sequence data, some of which come from tailless RNA. Last year, molecular biologist Julia Salzman of Stanford University School of Medicine and colleagues sent out the first letter from this circular universe. They reported that excessive amounts of circular human RNAs were found in the search for RNA that might be overlooked by traditional methods. When Rajewsky and colleagues explored a database of circular RNA molecules, they found thousands of circular RNAs in nematodes, mice, and humans. Sontheimer said: "This is another excellent example of an important RNA flying under the radar." Another independent research team led by Thomas Hansen and Jorgen Kjems of Aarhus University in Denmark completed the second Nature paper. the study. Both papers focus on a large circular RNA consisting of approximately 1500 nucleotides expressed in the brains of mice and humans. The researchers found that it contains 70 miR-7 binding sites. MicroRNAs are short RNAs that block gene expression by binding to and preventing mRNA translation. It has long been known that the target of MiR-7 is associated with cancer and Parkinson's disease. Hansen's team found that expression of this circular RNA blocked miR-7. It inhibits miR-7 activity and increases miR-7 target gene expression, which the researchers speculate is because this RNA loop captures and inactivates miR-7. The Rajewsky team confirmed that expression of this circular RNA in zebrafish or knockout of miR-7 can alter brain development. Rajewsky said that circular RNAs may also be sponges for extracellular microRNAs. Some may have binding sites for viral microRNAs, thereby damaging the immune response. Rajewsky speculated that circular RNA may even interact with RNA-binding proteins. Salzman agrees: "Their number is so rich that it may play multiple functional roles." So, are there other shapes for RNAs? "I don't think we might have missed other forms. But you know that someone will always find it. Phillip Sharp, a molecular biologist at the Massachusetts Institute of Technology in Cambridge, said with a smile.

Source: Biopass

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