Navigation Links
Human genes sing different tunes in different tissues

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
Massachusetts Institute of Technology

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. 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:
(Date:11/10/2015)... 10, 2015 About signature ... helps to identify and verify the identity of ... as the secure and accurate method of authentication ... particular individual because each individual,s signature is highly ... when dynamic signature of an individual is compared ...
(Date:11/9/2015)...  Synaptics Inc. (NASDAQ: SYNA ), the leading ... into the automotive market with a comprehensive and dedicated ... consumer electronics human interface innovation. Synaptics, industry-leading touch controllers, ... automotive industry and will be implemented in numerous locations ... , Japan , and ...
(Date:11/2/2015)...  SRI International has been awarded a contract of ... to the National Cancer Institute (NCI) PREVENT Cancer Program ... modern testing and support facilities, and analytical instrumentation to ... studies to evaluate potential cancer prevention drugs. ... Drug Development Program is an NCI-supported pipeline to bring ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... -- Cepheid (NASDAQ: CPHD ) today announced that ... and invited investors to participate via webcast. ... 1, 2015 at 11.00 a.m. Eastern Time --> ... 1, 2015 at 11.00 a.m. Eastern Time --> ... NY      Tuesday, December 1, 2015 at 11.00 ...
(Date:11/24/2015)... Nov. 24, 2015 /PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ: ... on behalf of the Toronto Stock Exchange, confirms that ... are no corporate developments that would cause the recent ... --> --> About Aeterna Zentaris Inc. ... --> Aeterna Zentaris is a specialty biopharmaceutical ...
(Date:11/24/2015)... , November 24, 2015 SHPG ) announced ... in the Piper Jaffray 27 th Annual Healthcare Conference in ... 1, 2015, at 8:30 a.m. EST (1:30 p.m. GMT). --> ... Financial Officer, will participate in the Piper Jaffray 27 th ... NY on Tuesday, December 1, 2015, at 8:30 a.m. EST (1:30 ...
(Date:11/24/2015)... ... 24, 2015 , ... In harsh industrial processes, the safety ... sensors can represent a weak spot where leaking process media is a possible ... housings , which are designed to tolerate extreme process conditions. They combine rugged ...
Breaking Biology Technology: