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
Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München
Second research flight into zero gravity
21.10.2016 | Universität Zürich
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences