Researchers discover a mechanism that enables SINEUPs to increase 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 making an important type of functional non-coding RNA known as SINEUPs promote their effects on Target Messenger -RNA.SINEUPs are a recently discovered type of RNA specifically designed to enhance the production of proteins by messenger RNAs and therefore could be important for the development of therapeutics for diseases in which a particular protein is not sufficiently synthesized.

While DNA was previously thought to be simply transcribed into RNA, which was then translated into proteins, it is now known that RNA plays a more complex role. While 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% play a role in improving gene expression, epigenetic regulation and – in the case of SINEUPs – upregulating the production of proteins by the target RNA.

The current research published in Nucleic acid researchstudies a specific type of non-coding RNA known as SINEUPs. These are essentially “genetic parasites” that have been incorporated into the genome as repeating elements. Although they are understood to potentiate the activity of the messenger RNAs with which they are associated, the mechanism behind that activity has remained a mystery.

Hazuki Takahashi of the RIKEN Center for Integrative Medical Sciences, one of the authors of the paper, said, “We wanted to find out the mechanism by which SINEUPs work. Understanding how these RNAs work would be a huge breakthrough because they exist. ”A number of diseases, caused by the failure of genes to produce sufficient amounts of a particular protein, and knowing how SINEUPs work, could be offer us a way to fix this. ”

The group had evidence from their previous research. They had found that the SINEUPs only affected the effect of their target messenger RNA if they were transported together with the messenger RNA from the cell nucleus into the cytosol, where protein production takes place.

Through a series of experiments with natural SINEUPs and artificial SINEUPs equipped with a fluorescent protein to allow the team to study their movements, they found that a pair of RNA-binding proteins, PTBP1 and HNRNPK, interacted with the SINEUPs, to enable their transport and to enable them to act on the messenger RNA. These two proteins are very interesting because they have been found to work together in a variety of biological functions such as maintaining the pluripotency of cells. They are also very important biologically as switching off the HNRNPK gene in mice has been shown to be embryonically fatal.

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

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