Navigation Links
Human genes sing different tunes in different tissues
Date:11/2/2008

CAMBRIDGE, Mass. -- Scientists have long known that it's possible for one gene to produce slightly different forms of the same protein by skipping or including certain sequences from the messenger RNA. Now, an MIT team has shown that this phenomenon, known as alternative splicing, is both far more prevalent and varies more between tissues than was previously believed.

Nearly all human genes, about 94 percent, generate more than one form of their protein products, the team reports in the Nov. 2 online edition of Nature. Scientists' previous estimates ranged from a few percent 10 years ago to 50-plus percent more recently.

"A decade ago, alternative splicing of a gene was considered unusual, exotic but it turns out that's not true at all it's a nearly universal feature of human genes," said Christopher Burge, senior author of the paper and the Whitehead Career Development Associate Professor of Biology and Biological Engineering at MIT.

Burge and his colleagues also found that in most cases the mRNA produced depends on the tissue where the gene is expressed. The work paves the way for future studies into the role of alternative proteins in specific tissues, including cancer cells.

They also found that different people's brains often differ in their expression of alternative spliced mRNA isoforms.

Human genes typically contain several "exons," or DNA sequences that code for amino acids, the building blocks of proteins. A single gene can produce multiple protein sequences, depending on which exons are included in the mRNA transcript, which carries instructions to the cell's protein-building machinery.

Two different forms of the same protein, known as isoforms, can have different, even completely opposite functions. For example, one protein may activate cell death pathways while its close relative promotes cell survival.

The researchers found that the type of isoform produced is often highly tissue-dependent. Certain protein isoforms that are common in heart tissue, for example, might be very rare in brain tissue, so that the alternative exon functions like a molecular switch. Scientists who study splicing have a general idea of how tissue-specificity may be achieved, but they have much less understanding of why isoforms display such tissue specificity, Burge said.

Scientists have also observed that cells express different isoforms during embryonic development and at different stages of cellular differentiation. Burge's team is now studying cells at various stages of differentiation to see when different isoforms are expressed.

Isoform switching also occurs in cancer cells. One such switch involves a metabolic enzyme and contributes to cancer cells burning large amounts of glucose and growing more rapidly. Learning more about such switches could lead to potential cancer therapies, Burge said.

Until now, it has been difficult to study isoforms on a genome-wide scale because of the high cost of sequencing and technical issues in discriminating similar mRNA isoforms using microarrays. The team took mRNA samples from 10 types of tissue and five cell lines from a total of 20 individuals, and generated more than 13 billion base pairs of sequence, the equivalent of more than four entire human genomes.

The sequencing was done by researchers at biotech firm Illumina, using a new high-throughput sequencing machine.


'/>"/>

Contact: Teresa Herbert
therbert@mit.edu
617-258-5403
Massachusetts Institute of Technology
Source:Eurekalert

Related biology news :

1. Similarities in imaging the human body, Earths crust focus of conference at UH
2. Researchers apply systems biology and glycomics to study human inflammatory diseases
3. UCSB study finds physical strength, fighting ability revealed in human faces
4. ICSU launches new program to understand the human impact on Earths life-support systems
5. Human protein atlas will help pinpoint disease
6. Genetic based human diseases are an ancient evolutionary legacy
7. The American Society of Human Genetics hosts 58th Annual Meeting in Philadelphia
8. Gene with probable role in human susceptibility to pulmonary tuberculosis identified
9. TheVisualMD.com launches new animated 3-D views of human body in action
10. Human Microbiome Project awards funds for technology development, data analysis and ethical research
11. Study: Bird diversity lessens human exposure to West Nile Virus
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/3/2017)... 3, 2017  Texas Biomedical Research Institute announced that its ... Schlesinger as the Institute,s new President and CEO. Dr. ... 31, 2017. He is currently the Chair of the Department ... for Microbial Interface Biology at Ohio State University. ... President and CEO of Texas Biomed," said Dr. James ...
(Date:2/2/2017)... , Feb. 2, 2017  EyeLock LLC, a market ... new white paper " What You Should Know About ... of ensuring user authenticity is a growing concern. In ... of users. However, traditional authentication schemes such as username/password ... Biometric authentication offers an elegant solution to the ...
(Date:1/31/2017)... 2017  Spero Therapeutics, LLC, a biopharmaceutical company ... of bacterial infections, today announced it has acquired ... Pro Bono Bio Ltd (PBB) to bolster its ... forms of Gram-negative bacteria.   The assets acquired have ... PBB group company. "The acquisition of ...
Breaking Biology News(10 mins):
(Date:2/23/2017)... 2017  Seattle,s upscale Capitol Hill neighborhood, with its swanky shops, ... a head lice treatment salon to set up shop. But ... and a French bistro on E Madison Ave, and CEO ... any old lice clinic, we pride ourselves on being a ... some of the stigma associated with lice. Everyone can get ...
(Date:2/23/2017)... ... February 23, 2017 , ... David Nolte, PhD ... Reception at Purdue Research Park of West Lafayette, Indiana. , The ... outstanding contributions to, and success with, commercializing discoveries from Purdue research. “This award ...
(Date:2/23/2017)... DIEGO , Feb. 23, 2017 ... research tools, announced the acquisition of GenWay Biotech ... a comprehensive service and product offering for both ... acquisition will facilitate growth and enhance capabilities for ... antibodies, and ELISA assays will nicely complement ASB,s ...
(Date:2/22/2017)... ... February 22, 2017 , ... ... has acquired Kendall Research Systems, LLC (KRS) clinical development program. KRS ... neural interface technology for research and clinical applications. The terms of the transaction ...
Breaking Biology Technology: