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:12/16/2016)... Research and Markets has announced the addition of the ... report to their offering. ... The biometric vehicle access system market, in terms of ... 2016 to 2021. The market is estimated to be USD 442.7 ... 2021. The growth of the biometric vehicle access system market is ...
(Date:12/15/2016)... , Dec. 15, 2016   WaferGen Bio-systems, Inc. ... genomics technology company, announced today that on December 13, ... Department of The Nasdaq Stock Market LLC which acknowledged ... price of WaferGen,s common stock had been at $1.00 ... has regained compliance with Listing Rule 5550(a)(2) of the ...
(Date:12/15/2016)... AUBURN HILLS, Mich. , Dec. 15, 2016 /PRNewswire/ ... simply unlocking car doors or starting the engine. Continental ... 2017 in Las Vegas . Through ... PASE (Passive Start and Entry) and biometric elements, the ... the field of vehicle personalization and authentication. ...
Breaking Biology News(10 mins):
(Date:1/19/2017)... BD (Becton, Dickinson and Company) (NYSE: BDX ), a ... live webcast of its Annual Meeting of Shareholders on Tuesday, January ... can be accessed from the BD corporate website at http://www.bd.com/investors/ ... ... BD is a global medical technology company that is ...
(Date:1/18/2017)... , Jan. 18, 2017   Boston Biomedical ... compounds designed to target cancer stemness pathways, will feature ... compound, napabucasin, at the 2017 ASCO Gastrointestinal Cancers Symposium, ... . Napabucasin is an orally-administered ... targeting STAT3. i Cancer stem cells (CSCs) possess ...
(Date:1/18/2017)... (PRWEB) , ... January 18, 2017 , ... ... for Clinical Ops Executives 2017 in its continued commitment to the advancement of ... makers to discuss current issues related to clinical trial planning and management. ...
(Date:1/18/2017)... ... January 18, 2017 , ... Announced in December ... Institutes (MII). U.S. Secretary of Commerce Penny Pritzker has announced the award of ... of Defense has announced the award of a new Advanced Regenerative Manufacturing Institute ...
Breaking Biology Technology: