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
Discovery of a Key Regulatory Gene in Cardiac Valve Formation
24.05.2017 | Universität Basel
Carcinogenic soot particles from GDI engines
24.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
24.05.2017 | Physics and Astronomy
24.05.2017 | Physics and Astronomy
24.05.2017 | Event News