Singapore Scientists Discover New RNA Processing Pathway Important in Human Embryonic Stem Cells

12-Sep-2013 - Singapore

Scientists at A*STAR's Genome Institute of Singapore (GIS), in collaboration with their counterparts from Canada, Hong Kong and US, have discovered a protein mediator SON plays a critical role in the health and proper functioning of human embryonic stem cells (hESCs). This finding was reported in Nature Cell Biology.

Correct expression of genes is essential for a cell to stay alive and to perform other cellular and physiological functions. During gene expression, DNA is first converted into RNA transcript and then some parts of it are removed while others are joined before the trimmed RNA transcript can be translated into proteins. This process of cutting and joining different pieces of RNA is called splicing, and the proteins that mediate splicing are known as splicing factors. Mutations in splicing factors can cause diseases such as myotonic dystrophy and cancer. Even though hESCs have been studied extensively over the last decade due to their potential to differentiate into cell-types of potential clinical applications, little is known about the role that splicing plays in the regulation of pluripotency in these cells.

Scientists at the GIS followed their previous study on a genome-wide investigation of gene functions in hESCs and found that splicing factors, such as the protein known as SON, are key regulators of hESC maintenance.

SON was discovered to be essential for converting differentiated cells into pluripotent stem cells. In addition, SON promotes correct splicing of a particular group of RNAs, including those coding for essential hESC regulators, and thereby helps hESCs to survive in an undifferentiated state. Moreover, the authors showed that silencing of SON induced new transcript isoforms that seemed to be non-functional in hESCs.

The study, led by GIS Executive Director Prof Ng Huck Hui, establishes an initial connection between splicing and pluripotency in hESCs and contributes to the comprehensive understanding of the nature of hESCs. Besides its role in hESCs, SON was previously found to be involved in the development of leukemia and influenza virus infection.

Original publication

Xinyi Lu, Jonathan Goke, Friedrich Sachs, Pierre-Etienne Jacques, Hongqing Liang, Bo Feng, Guillaume Bourque, Paula A. Bubulya, Huck-Hui Ng; "SON connects the splicing-regulatory network with pluripotency in human embryonic stem cells."; Nature Cell Biology 2013.

https://www.bionity.com/en/news/144908/singapore-scientists-discover-new-rna-processing-pathway-important-in-human-embryonic-stem-cells.html