Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The Splice of Life: Proteins Cooperate to Regulate Gene Splicing

17.02.2012
Understanding how RNA binding proteins control the genetic splicing code is fundamental to human biology and disease – much like editing film can change a movie scene. Abnormal variations in splicing are often implicated in cancer and genetic neurodegenerative disorders.

In a step toward deciphering the “splicing code” of the human genome, researchers at the University of California, San Diego School of Medicine have comprehensively analyzed six of the more highly expressed RNA binding proteins collectively known as heterogeneous nuclear ribonucleoparticle (hnRNP) proteins.


UC San Diego School of Medicine
RNAs wound in a knot and bound by hnRNP proteins illustrates the intractable problem of RNA regulation addressed by Huelga et al.

This study, published online Feb 16 in Cell Press’ new open-access journal Cell Reports, describes how multiple RNA binding proteins cooperatively control the diversity of proteins in human cells by regulating the alternative splicing of thousands of genes.

In the splicing process, fragments that do not typically code for protein, called introns, are removed from gene transcripts, and the remaining sequences, called exons, are reconnected. The proteins that bind to RNA are important for the control of the splicing process, and the location where they bind dictates which pieces of the RNA are included or excluded in the final gene transcript -- in much the same fashion that removing and inserting scenes, or splicing, can alter the plot of a movie.

“By integrating vast amounts of information about these key binding proteins, and making this data widely available, we hope to provide a foundation for building predictive models for splicing and future studies in other cell types such as embryonic stem cells,” said principal investigator Gene Yeo, PhD, assistant professor in the Department of Cellular and Molecular Medicine and the Institute for Genomic Medicine at UC San Diego, and a visiting professor at the Molecular Engineering Laboratory in Singapore. “If we can understand how these proteins work together and affect one another to regulate alternative splicing, it may offer important clues for rational drug design.”

The data sets highlighted in this study – derived from genome-wide methods including custom-designed splicing-sensitive microarrays, RNA sequencing and high-throughput sequencing to identify genome-wide binding sites (CLIP-seq) -- map the functional binding sites for six of the major hnRNP proteins in human cells.

“We identified thousands of binding sites and altered splicing events for these hnRNP proteins and discovered that, surprisingly these proteins bind and regulate each other and a whole network of other RNA binding proteins, suggesting that these proteins are important for the homeostasis of the cell,” said first author, NSF fellow Stephanie C. Huelga.

According to the UCSD researchers, the genes specifically targeted by the RNA binding proteins in this study are also often implicated in cancer. Yeo added that of the thousands of genomic mutations that appear in cancer, a vast majority occur in the introns that are removed during splicing; however, intronic regions are where regulatory hnRNP proteins often bind.

“Our findings show an unprecedented degree of complexity and compensatory relationships among hnRNP proteins and their splicing targets that likely confer robustness to cells. The orchestration of RNA binding proteins is not only important for the homeostasis of the cell, but – by mapping the location of binding sites and all the regulatory places in a gene – this study could reveal how disruption of the process leads to disease and, perhaps, a way to intervene.”

Additional contributors to the study include Anthony Q. Vu, Justin D. Arnold, Tiffany Y. Liang, Patrick P. Liu and Bernice Y. Yan, UCSD Cellular and Molecular Medicine; John Paul Donohue, Lily Shiue and Manuel Ares, Jr., UC Santa Cruz; Shawn Hoon and Sydney Brenner, A*STAR, Singapore.

The study was funded in part by grants from the National Institutes of Health and the UC San Diego Stem Cell Research Program.

Debra Kain | Newswise Science News
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht Fingerprint' technique spots frog populations at risk from pollution
27.03.2017 | Lancaster University

nachricht Parallel computation provides deeper insight into brain function
27.03.2017 | Okinawa Institute of Science and Technology (OIST) Graduate University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Northern oceans pumped CO2 into the atmosphere

27.03.2017 | Earth Sciences

Fingerprint' technique spots frog populations at risk from pollution

27.03.2017 | Life Sciences

Big data approach to predict protein structure

27.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>