As reported in a study published online ahead of print on December 19 in Nature Cell Biology, the scientists discovered this unique structure-building role for the RNAs by keeping a close watch on them from the moment they come into existence within a cell's nucleus. The scientists' visual surveillance revealed that when the genes for these RNAs are switched on, and the RNAs are made, they recruit other RNA and protein components and serve as a scaffolding platform upon which these components assemble to form paraspeckles.
The two RNAs described in the study, named MENå and MENâ, are "non-coding" RNAs —a type of RNA that does not serve as a code or template for the synthesis of cellular proteins. The genes that give rise to these non-coding RNAs are now thought to make up most of the human genome, in contrast to the genes that produce protein-coding RNAs, which account for approximately 2% of the human genome.
"We've known for several years that much of the other 98% of the genome doesn't encode for useless RNA," explains CSHL's Professor David L. Spector, who led the current study. "Various types of non-coding RNAs have been found that regulate the activity of protein-coding genes and cellular physiology in different ways. Our results reveal a new and intriguing function for a non-coding RNA—the ability to trigger the assembly and maintenance of a nuclear body."
The nuclear bodies in question—the paraspeckles—are believed to serve as nuclear storage depots for RNAs that are ready to be coded, or translated, into proteins but are retained in the cell nucleus. Paraspeckles are thought to release this RNA cache into the cell's cytoplasm—the site of protein synthesis—under certain physiological conditions, such as cellular stress. Spector estimates that storing pre-made protein-coding RNA within the paraspeckles and releasing them as needed allows the cell to respond faster than if it had to make the RNA from scratch.
Previous experiments by Spector's team and two other groups indicated that MENå and MENâ RNAs were the critical elements for paraspeckle formation. "What wasn't clear was how the paraspeckles actually form and the dynamics of how the non-coding MEN RNAs help organize and maintain its structure," says Spector.
To address this question, the team developed an innovative approach—spearheaded by CSHL postdoctoral fellow Yuntao (Steve) Mao and graduate student Hongjae Sunwoo—to peer into living cells and capture the real-time dynamics of the interactions among the set of molecules known to be involved in paraspeckle formation. The scientists engineered cells in which each of these players—the MENå/â genes, the newly formed MEN RNAs, and the various paraspeckle protein components—each carried a different colored fluorescent tag. The cells were also genetically manipulated such that the MEN genes could be switched on by exposing the cells to a drug.
The resulting movies shot by the Spector team, showed that within five minutes of switching on the MENå/â gene, individual paraspeckle proteins arrived and assembled at the sites of MEN RNA transcription. As the RNA transcripts accumulated, the fully functional paraspeckles enlarged in tandem and eventually broke away to cluster around the transcription sites.
"Our experiments show that it is the act of MEN RNA transcription alone that triggers paraspeckle formation and sustains them," says Spector. In the absence of transcriptional activity—such as during cell division or when the scientists added drugs that block RNA transcription or specifically switched off the MEN genes—the newly formed paraspeckles fell apart.
This dependency on RNA transcription seems to be unique, as other nuclear compartments such as Cajal bodies can form when one of their components is simply tethered to a site on the genome, which in turn causes other components to coalesce around it. In contrast, says Spector, "Paraspeckles seem to follow a different assembly model in which MEN non-coding RNAs serve as seeding molecules that are driven by transcription to recruit the other components."
This work was supported by grants from the National Institute of General Medical Sciences, one of the National Institutes of Health.
"Direct visualization of the co-transcriptional assembly of a nuclear body by noncoding RNAs," is embargoed until 1pm EST on December 19 and will appear online ahead of print in Nature Cell Biology. The full citation is: Yuntao S. Mao, Hongjae Sunwoo, Bin Zhang, and David L. Spector.
Hema Bashyam | EurekAlert!
Cloud Formation: How Feldspar Acts as Ice Nucleus
09.12.2016 | Karlsruher Institut für Technologie
Closing the carbon loop
08.12.2016 | University of Pittsburgh
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
08.12.2016 | Life Sciences
08.12.2016 | Physics and Astronomy
08.12.2016 | Materials Sciences