Navigation Links
Singapore scientists discover new RNA processing pathway important in human embryonic stem cells
Date:9/9/2013

09 Sept 2013 - 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 on 8th September 2013 in the advanced online issue of the prestigious science journal 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, which was published in Nature [Chia et al. 2010. 468(7321):316-20], 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.

Prof Ng Huck Hui said, "Maintenance and differentiation of human embryonic stem cells are governed by an intricate network that comprises diverse cellular processes. In the past, we had been focusing primarily on transcriptional regulation. In our new study, it is clear that splicing contributes to the unique cellular state of hESCs and this can be explained in part through the function of a protein known as SON. SON regulates the precise splicing of specific transcripts which are important for pluripotency. A systematic dissection of the different pathways required for maintenance of pluripotency can eventually guide us in engineering novel cellular states in the laboratory."

"In this new manuscript in Nature Cell Biology, Ng Huck Hui and his colleagues continue to cement their position at the forefront of pluripotency research worldwide," said Dr Alan Colman, the former Executive Director of the Singapore Stem Cell Consortium. "The distinctive feature of human embryonic stem cells is their ability to either self renew or alternatively, given the right conditions, to differentiate into all the cell types that comprise the adult body. In previous work, the team had uncovered a number of unique transcription factors that mediate the maintenance of pluripotency via binding to genomic DNA. In this latest publication, they reveal a novel mechanism where SON, a protein localized to nuclear speckles, regulates the proper splicing of transcripts encoding pluripotency regulators such as OCT4, PRDM14, E4F1 and MED24, and ensures cell survival and maintenance of pluripotency in hESC (and by extrapolation, presumably human induced pluripotent stem cells also)."

Prof Eran Meshorer from the Department of Genetics at the Hebrew University of Jerusalem added, "In recent years, a growing number of papers focusing on the transcriptional regulators that control embryonic stem cell biology have been published. However, the link between RNA splicing and pluripotency has only very recently emerged and the factors that regulate splicing and alternative splicing in ES cells are unknown. The paper by Ng Huck Hui and colleagues now shows that the splicing regulator SON, previously identified in a screen conducted by the same group for novel pluripotency-related factors, regulates the splicing of several key pluripotency genes, linking splicing with stem cell biology and pluripotency. This paper provides a major step towards a more complete understanding of the mechanisms controlling pluripotency and self-renewal, and calls for the identification of additional splicing regulators in ES cells. It is also tempting to speculate that SON and other splicing-related proteins may assist in converting somatic cells into pluripotent cells in the process of reprogramming." Prof Meshorer is the winner of the 2013 Sir Zelman Cowen Universities Fund Prize for Medical Research for the extensive and groundbreaking work undertaken in his laboratory to shed light on pluripotency.


'/>"/>

Contact: Winnie Lim
limcp2@gis.a-star.edu.sg
65-680-88013
Agency for Science, Technology and Research (A*STAR), Singapore
Source:Eurekalert

Related biology news :

1. Made-in-Singapore H5N1 diagnostic kit -- detects all known strains of H5N1 virus with a single test
2. NUS launches new book on Singapores rainforests and new free digital nature archive
3. Singapore scientists find genes associated with glaucoma, a major cause of eye blindness
4. National Heart Centre Singapore develops worlds first human heart cell model
5. First in the world - Singapore scientists discover genes responsible for cornea blindness
6. Singapore research team identifies new drug target in deadly form of leukemia
7. Less haze in Singapore as the cause becomes clearer and more complex
8. Physiotherapy in Singapore Clinic Urbanrehab Pte Ltd Announces the Opening of an Additional Location
9. Stanford scientists develop gene therapy approach to grow blood vessels in ischemic limbs
10. Queens scientists seek vaccine for Pseudomonas infection
11. Scientists produce eye structures from human blood-derived stem cells
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/13/2018)... ... December 12, 2018 , ... NDA Partners Chief Executive Officer ... Expert Consultants, was recently honored by the American Association of Pharmaceutical Scientists (AAPS) ... pharmaceutical science, technology, engineering, or education and whose contributions to the pharmaceutical sciences ...
(Date:12/10/2018)... (PRWEB) , ... December 10, 2018 , ... Nanomedical ... announces a headquarters relocation to 9640 Towne Centre Drive, Suite 100, effectively tripling its ... exponential growth, both domestically and internationally, for the sales of our drug discovery platforms. ...
(Date:12/5/2018)... ... December 03, 2018 , ... uBiome, the leader in ... in the Division of Gastroenterology and Hepatology at UC San Diego and staff ... Joining the board of leading scientists and doctors from around the world, Dr. ...
Breaking Biology News(10 mins):
(Date:12/5/2018)... SAN DIEGO (PRWEB) , ... December 05, 2018 , ... ... Itzkowich, introduces an all-new, how-to guide with his “The Referral Playbook: How to ... Itzkowich, 100% of the book proceeds will go to the Alzheimer’s Foundation of America ...
(Date:11/29/2018)... , ... November 29, 2018 , ... RAGS, today announced ... by Kickstart Seed Fund, with participation from existing investor and board member Jeremy Andrus, ... Smith of Cotopaxi. The additional funding will enable the company to accelerate its growth ...
(Date:11/20/2018)... ... November 19, 2018 , ... The International Society ... the Chinese translation of Best Practices: Recommendations for Repositories, Fourth Edition. , The ... at advancing the science of biobanking to meet the needs of a growing ...
(Date:11/15/2018)... ... November 14, 2018 , ... ... self-learning snore-reduction mask to the public. It is estimated that 90 million ... for themselves and their partner. The resulting daytime fatigue causes extreme difficulty with ...
Breaking Biology Technology: