Navigation Links
New mechanism for human gene expression discovered
Date:7/4/2013

In a study that could change the way scientists view the process of protein production in humans, University of Chicago researchers have found a single gene that encodes two separate proteins from the same sequence of messenger RNA.

Published online July 3 in Cell, their finding elucidates a previously unknown mechanism in human gene expression and opens the door for new therapeutic strategies against a thus-far untreatable neurological disease.

"This is the first example of a mechanism in a higher organism in which one gene creates two proteins from the same mRNA transcript, simultaneously," said Christopher Gomez, MD, PHD, professor and chairman of the Department of Neurology at the University of Chicago, who led the study. "It represents a paradigm shift in our understanding of how genes ultimately encode proteins."

The human genome contains a similar number of protein-coding genes as the nematode worm (roughly 20,000). This disparity between biological complexity and gene count partially can be explained by the fact that individual genes can encode multiple protein variants via the production of different sequences of messenger RNA (mRNA)short, mass-produced copies of genetic code that guide the creation of myriad cellular machinery.

Gomez and his team, which included first author Xiaofei Du, MD, discovered a new layer of complexity in this process of gene expression as they studied spinocerebellar ataxia type-6 (SCA6), a neurodegenerative disease that causes patients to slowly lose coordination of their muscles and eventually their ability to speak and stand. Human genetic studies identified its cause as a mutation in CACNA1Aa gene that encodes a calcium channel protein important for nerve cell functionresulting in extra copies of the amino acid glutamine.

However, although the gene, mutation and dysfunction are known, attempts to find the biological mechanism of the disease proved inconclusive. Calcium channel proteins with the mutation still seemed to function normally.

Suspecting another factor at play, Gomez and his team instead focused on α1ACT, a poorly understood, free-floating fragment of the CACNA1A calcium channel protein known to express extra copies of glutamine in SCA6 cells. The researchers first looked at its origin and found that, to their surprise, α1ACT was generated from the same mRNA sequence as the CACNA1A calcium channel.

For the first time, they had evidence of a human gene that coded one strand of mRNA that coded two separate, structurally distinct proteins. This occurred due to the presence of a special sequence in the mRNA known as an internal ribosomal entry site (IRES). Normally found at the beginning of an mRNA sequence, this IRES site sat in the middle, creating a second location for ribosomes, the cellular machines that read mRNA, to begin the process of protein production.

Looking at function, Gomez and his team found that normal α1ACT acted as a transcription factor and enhanced the growth of specific brain cells. Importantly, mutated α1ACT appeared to be toxic to nerve cells in a petri dish, and caused SCA6-like symptoms in an animal model.

The team hopes to discover other examples of human genes with similar IRES sites to better understand the implications of this new class of "bifunctional" genes on our basic biology. For now, they are focused on leveraging their findings toward helping SCA6 patients and already are working on ways to silence mutated α1ACT.

"We discovered this genetic phenomenon in the pursuit of a disease cause and, in finding it, immediately have a potential strategy for developing preclinical tools to treat that disease," Gomez said. "If we can target the IRES and inhibit production of this mutant form of α1ACT in SCA6, we may be able to stop the progression of the disease."


'/>"/>

Contact: Kevin Jiang
kevin.jiang@uchospitals.edu
773-795-5227
University of Chicago Medical Center
Source:Eurekalert

Related biology technology :

1. UCSB researchers identify the mechanisms underlying salt-mediated behaviors in fruit flies
2. Understanding the molecular mechanisms underlying Alzheimers disease
3. Inflamax Research selected by the Immune Tolerance Network and the National Institutes of Health to conduct a landmark clinical study on the underlying mechanisms of allergic inflammation.
4. Penn research shows mechanism behind wear at the atomic scale
5. SomaGenics Reports Study on Mechanism of Action of Its Therapeutic Platform
6. Drexels Gogotsi and team advance understanding of energy storage mechanisms in Nature Materials
7. Nutra Pharma Announces Publication of a New Mechanism Study of Alpha-Cobratoxin in the Treatment of Pain
8. A New Mechanism for Tau Protein Pathology in Alzheimers Disease was Presented by Oligomerix, Inc. at the Society for Neuroscience Annual Meeting
9. Sorrento Therapeutics Presents Preclinical Data of its Fully Human Antibody Programs Targeting Anti-PD-L1 and Anti-PD-1 at the 8th Annual Next Generation Protein Therapeutics Summit
10. PROLOR Biotech To Present New Data On Its Long-Acting Human Growth Hormone And Long-Acting Oxyntomodulin At ENDO 2013
11. ChanTest Develops New Cardiotoxicity and Contractility Assay with Human Stem Cell Cardiomyocytes
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/8/2016)... ... 2016 , ... Franz Inc. , an early innovator ... announced the availability of AllegroGraph 6, the leading Semantic Graph Database with certification ... Program (CCPT). AllegroGraph is the first Semantic Graph Database to be certified ...
(Date:2/8/2016)... England , February 8, 2016 ... Ltd ("Atlas Genetics" or the "Company"), the ultra-rapid Point-Of-Care (POC) ... to CE Mark its Chlamydia trachomatis (CT) test to be ... of the IVD Directive (98/79/EC), the CT test is now ... --> --> The launch of the io® ...
(Date:2/5/2016)... Feb. 5, 2016  In the pharmaceutical industry the ... host of launch activities including the identification and engagement ... activity is especially high in the oncology therapeutic area ... Practices and the Role of Medical Affairs in Oncology ... on oncology therapies find better ways to utilize medical ...
(Date:2/4/2016)... ... February 04, 2016 , ... Morf ... today announced an interactive FDA compliance training course, Writing Effective ... Professional Society) accredited interactive course on Morf Playbook—now conveniently available on smartphones and ...
Breaking Biology Technology:
(Date:1/25/2016)... , Jan. 25, 2016  Glencoe Software, the ... pharma and publication industries, will provide the data management ... Centre (NPSC). ... Phenotypic analysis measures ... whole organisms, allowing comparisons between states such as health ...
(Date:1/20/2016)... 2016   MedNet Solutions , an innovative SaaS-based ... clinical research, is pleased to announce the attainment of ... the result of the company,s laser focus on (and ... , it,s comprehensive, easy-to-use and highly affordable cloud-based technology ... Key MedNet growth achievements in 2015 include: ...
(Date:1/13/2016)... January 13, 2016 ... addition of the  "India Biometrics Authentication ... Forecast (2015-2020)"  report to their ... has announced the addition of the  ... - Estimation & Forecast (2015-2020)" ...
Breaking Biology News(10 mins):