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Monday October 08th, 2012

IDIBAPS researchers discover how a new type of RNA is related with diabetes

IDIBAPS - Programació Genòmica de Cèl·lules Beta i Diabetis

Complex diseases such as diabetes are usually not caused by a single gene. These pathologies produced by a complex genetic equilibrium that is slowly described thanks to new genomic analysis technologies. A study led by researchers at the Institut d’Investigacions Biomèdiqes August Pi i Sunyer (IDIBAPS) shows that a new type of RNA, the long non-coding RNA (lncRNA), is related to the most common form of diabetes, Type 2 diabetes. It also is important in cell maturation, participating in the formation of pancreatic beta cells in embryos.

The results obtained with both human cells and animal models, identify new genes specific for beta cells, demonstrating for the first time an association between lncRNA and diabetes. They also provide valuable information for researchers working to produce in vitro pancreatic beta cells available for transplantation. A more detailed analysis of the results, which is already in process by IDIBAPS researchers, could identify new therapeutic targets to help fight diabetes.

The researcher Ignasi Morán and Dr. Íldem Akerman are the first authors of the study, both from the IDIBAPS Genomic Programming of Beta Cells and Diabetes led by Dr. Jorge Ferrer. The research has been published in the journal Cell Metabolism and has been conducted inside the CIBER of metabolic diseases and diabetes (CIBERDEM), with the collaboration of prestigious international institutions like The Wellcome Trust Centre for Human Genetics at the University of Oxford, the University of California at San Diego and the University Pierre et Marie Curie – INSERM, among others.

A new type of RNA

The dogma of genetics is that genes in the DNA are transcribed into messenger RNA (mRNA) which is translated into proteins. There are other forms of RNA such as ribosomal RNA (rRNA) or transfer RNA (tRNA), which catalyze biological reactions, control gene expression or interact with signalling cascades within the cell. In recent years a new form of RNA has been described, the lncRNA. This is a molecule present in different parts of the cell that is not translated into protein.

The lncRNA are RNA long chains encoded in the genome. They are therefore genes outside classical genes, as these are traditionally associated with the production of proteins. Its function is still unknown, although it has been shown that lncRNA can be very tissue- specific and in some cases they have been associated with cancer, cell cycle, RNAs assembly or transcriptional regulation.

Therapeutic targets and clues for in vitro the production of pancreatic cells

IDIBAPS researchers from the Genomic Programming of Beta Cells and Diabetes team have analyzed in depth the lncRNAs of pancreatic beta cells that secrete insulin. They have identified genes that encode 1,128 lncRNAs, about half of which are specific for pancreatic cells. Many of them had not been described so far.

Although it is necessary to further study these data, the paper published in Cell Metabolism shows that at least one of these lncRNA regulates the expression of the GLIS3 gene, closely related to diabetes. This indicates that at least some of these lncRNA genes play regulatory roles. Furthermore, the DNA encoding some of these lncRNAs is localized in genome areas that contain variations of the DNA sequence which confer susceptibility to diabetes. This turns them into potential therapeutic targets. Finally, some lncRNA are produced in larger or smaller amounts than expected in beta cells of people with type 2 diabetes. These anomalies could be related to the beta cell abnormalities that cause this type of diabetes.

According to the study, the presence of these lncRNA increases during embryonic development. Its concentration reaches the higher levels when the pancreatic cells are already differentiated. These tissue specific molecules play an important role in cell maturation. Thus, they may have applications in the in vitro production of pancreatic cells for transplantation, an experimental therapy in development.

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