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Scientists From Genome Institute of Singapore And Stanford University Show RNA Architecture Expanding Our Understanding Of Human Genetics


2/4/2014 8:26:10 AM

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7th February 2014, Singapore - Scientists at A*STAR’s Genome Institute of Singapore (GIS) and the US-based Stanford University’s School of Medicine have successfully produced one of the first ever genome-wide views of Ribonucleic acid (RNA) shape patterns in humans. The visualisation of RNA shape paves the way for scientists to better understand the basis of human mutations, the impact of gene regulation and the causes of diseases. The study was reported in the 30th January 2014 issue of the scientific journal, Nature.

RNA is one of the major molecules in the cell that functions by folding into complex shapes. Not much is known as to why disruptions in RNA folding from mutations affect RNA’s shape and function. Disruptions in RNA shape in human transcriptomes1 can have serious consequences towards human health, with implications in cancer and other genetic diseases. While many mutations are known to be the cause of diseases, not much is known about mutations that stems from affected RNA shapes.

GIS Fellow and first author Dr Wan Yue said, “Studying the impact of human variations on global RNA structure is the first step towards understanding the contribution of structural mutations in human diseases.” Professor Sir David Lane, A*STAR Chief Scientist stressed the significance of Dr Wan Yue’s research, “Today, scientists around the world are rapidly realising the significant impact of RNA mutation on human health. The GIS study on RNA shape patterns leads the global charge among scientists in unravelling the mystery linking RNA mutation to the causes of diseases.”

Scientists have long been interested in the function of the RNA and on its ability to fold into diverse shapes to execute their respective functions. However, RNA structure probing had been a slow and tedious process, taking many days to obtain the secondary structure of a single RNA. In order to understand the nature of many RNAs in a cell, structure probing has to be done across hundreds or thousands of RNAs over a short time - a task previously thought impossible. The scientists at GIS and Stanford made it possible by scaling up RNA structure probing with the coupling of tradition probing and engaging a unique high throughput sequencing technology that allowed tens of thousands of nucleotides to be read simultaneously.

As thousands of RNA shapes were analysed, the scientists were able to identify many shape patterns vital for post-transcriptional RNA regulatory activities. The results show that around 15 per cent of mutations in the human transcriptome caused alterations in RNA shapes – a much higher percentage than previously estimated.

Prof Howard Chang of the Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, and lead author of the study, added, “This work shows that gene differences that change RNA shape are far more prevalent than previously appreciated, and may be involved in many human diseases.”

The study was also done in collaboration with researchers from the Weizmann Institute of Science in Israel.

Research publication:

The research findings described in the press release have been published in Nature on 30th January, 2014 under the title “Landscape and variation of RNA secondary structure across the human transcriptome”.

Authors:

Yue Wan1,2*, Kun Qu1*, Qiangfeng Cliff Zhang1, Ryan A. Flynn1, Ohad Manor3, Zhengqing Ouyang1,4, Jiajing Zhang1, Robert C. Spitale1, Michael P. Snyder5, Eran Segal3 and Howard Y. Chang1

1. Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
2. Genome Institute of Singapore, Singapore 138672
3. Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovet 76100, Israel.
4. Current address: The Jackson Laboratory for Genomic Medicine, 263 Farmington Avenue, ASB Call Box 901Farmington, CT 06030. USA.
5. Department of Genetics, Stanford University School of Medicine, Stanford, CA, 94305.
* These authors contributed equally.

Correspondence to: Yue Wan at wany@gis.a-star.edu.sg
Howard Chang at howchang@stanford.edu

For media queries and clarifications, please contact:
(Ms) Winnie Lim
Genome Institute of Singapore
Office of Corporate Communications
Tel: (65) 6808 8013
Email: limcp2@gis.a-star.edu.sg

About the Genome Institute of Singapore (GIS)

The Genome Institute of Singapore (GIS) is an institute of the Agency for Science, Technology and Research (A*STAR). It has a global vision that seeks to use genomic sciences to improve public health and public prosperity. Established in 2001 as a centre for genomic discovery, the GIS will pursue the integration of technology, genetics and biology towards the goal of individualized medicine.

The key research areas at the GIS include Human Genetics, Infectious Diseases, Cancer Therapeutics and Stratified Oncology, Stem Cell and Developmental Biology, Cancer Stem Cell Biology, Genomic Technologies, Computational and Systems Biology, and Translational Technologies.

The genomics infrastructure at the GIS is utilized to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.

For more information about GIS, please visit: www.gis.a-star.edu.sg

About the Agency for Science, Technology and Research (A*STAR)

The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that fosters world-class scientific research and talent to drive economic growth and transform Singapore into a vibrant knowledge-based and innovation driven economy.

In line with its mission-oriented mandate, A*STAR spearheads research and development in fields that are essential to growing Singapore’s manufacturing sector and catalysing new growth industries. A*STAR supports these economic clusters by providing intellectual, human and industrial capital to its partners in industry.

A*STAR oversees 18 biomedical sciences and physical sciences and engineering research entities, located in Biopolis and Fusionopolis, as well as their vicinity. These two R&D hubs house a bustling and diverse community of local and international research scientists and engineers from A*STAR’s research entities as well as a growing number of corporate laboratories.

For more information about A*STAR, please visit: www.a-star.edu.sg

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