Researchers discover the mechanism that allows SINEUPs to amplify protein production


Scientists from an international group led by the RIKEN Center for Integrative Medical Sciences and Yokohama City University have found that a pair of proteins plays a key role in allowing an important type of functional non-coding RNA, known as SINEUPs, to act to promote its target messenger RNA . SINEUPs are a type of recently discovered RNA that works specifically to amplify the production of proteins by messenger RNAs and, therefore, can be important for the development of therapies for diseases in which a certain protein is insufficiently synthesized.

Although it was believed that DNA was simply transcribed into RNA, which was then translated into proteins, it is now known that RNA plays a more complex role. Although almost all of the DNA is transcribed into RNA, it turns out that only 30% of the RNA is translated into proteins. The remaining 70% perform functions such as increased gene expression, epigenetic regulation and – in the case of SINEUPs – positive regulation of protein production by the target RNA.

Current research, published in Nucleic acid research, looks for a particular type of non-coding RNA, known as SINEUPs. These are essentially “genetic parasites” that have been incorporated as repeated elements in the genome. While it is understood that they work to amplify the activity of the messenger RNAs with which they are associated, the mechanism behind this activity has remained a mystery.

According to Hazuki Takahashi of the RIKEN Center for Integrative Medical Sciences, one of the corresponding authors of the article, “We wanted to discover the mechanism of action of SINEUPs. Understanding how these RNAs work would be a major step forward, because there are a number of diseases caused by failure of genes in creating sufficient amounts of a particular protein, and knowing how SINEUPs work could provide us with a way to remedy that. ”

The group had clues from their previous research. They noted that SINEUPs only affect the action of their target messenger RNA when they are transported, along with messenger RNA, out of the cell nucleus and into the cytosol where the protein is produced.

Through a series of experiments involving natural SINEUPs and artificial SINEUPs equipped with a fluorescent protein to allow the team to examine their movements, they found that a pair of RNA binding proteins, called PTBP1 and HNRNPK, interact with SINEUPs to allow their transport and enable them to act on messenger RNA. These two proteins are quite interesting, as they have found that they work together in a variety of biological functions, such as maintaining cell pluripotency. They are also biologically very important, as the knockout of the HNRNPK gene in mice has been shown to be lethal embryonic.

According to Piero Carninci of the RIKEN Center for Integrative Medical Sciences, leader of the research group, “We are delighted to have discovered the role of these binding proteins in the activities of SINEUPs. Due to SINEUPs’ ability to specifically modulate the translation of targeted mRNAs as needed, they are ideal for future therapies in humans where increasing the level of a specific protein could have a therapeutic effect.There are hundreds of diseases that would benefit from SINEUPs treatments, caused by the deficiency of a functional copy of a gene: these diseases are known under the general terms of haploinsufficiencies, and SINEUPs have the potential to increase the production of antibodies currently limited Understanding the mechanism of SINEUPs and other mechanisms of functional long non-coding RNAs is a very important first step for future applications these RNAs to improve human health. ”


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