Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Penn Study Identifies Molecular Guardian of Cell's RNA

When most genes are transcribed, the nascent RNAs they produce are not quite ready to be translated into proteins - they have to be processed first.

One of those processes is called splicing, a mechanism by which non-coding gene sequences are removed and the remaining protein-coding sequences are joined together to form a final, mature messenger RNA (mRNA), which contains the recipe for making a protein.

For years, researchers have understood the roles played by the molecular machines that carry out the splicing process. But, as it turns out, one of those familiar components plays a new, and altogether unexpected role.

As senior author Gideon Dreyfuss, PhD, the Isaac Norris Professor of Biochemistry and Biophysics at the University of Pennsylvania School of Medicine and colleagues report in Nature, one of the splicing machinery's components called U1 has a second, equally important role in gene expression: To enable gene sequences to be read out into their RNA transcripts in their entirety, rather than have that process prematurely stopped. Dreyfuss is also a Howard Hughes Medical Institute Investigator.

The researchers revealed an unexpected function for U1 in protecting mRNA transcripts from premature termination in addition to and independent of its role in splicing.

As Dreyfuss puts it, "U1 is a guardian of the transcriptome." The transcriptome is the set of all RNA molecules in one cell.

U1 is one of a collection of RNA-protein complexes, called snRNPs, that recognize splicing junctions, excise non-coding gene sequences called introns, and join the remaining coding sequences called exons together. The Dreyfuss team previously showed that loss of SMN, a protein that helps assemble snRNPs and is deficient in individuals with the common neurodegenerative disease spinal muscular atrophy (SMA), results in altered snRNP levels and abnormal splicing.

SMN deficiency affects all snRNPs to one degree or another. The Dreyfuss team wanted to find out what would happen if just one snRNP was missing. They started with U1.

The team's expectation was that they would detect an increase in unspliced RNA transcripts, and indeed they saw evidence of that. But, to their surprise, the majority of the genes produced a very different and striking result. Their transcripts terminated prematurely and abruptly, generally within a relatively short distance from the transcription start site of the gene.

When they sequenced the ends of the resulting truncated RNAs, they found that they had been prematurely cleaved and tagged with a long string of nucleotide building blocks called adenine. This string is a hallmark of a process called cleavage-and-polyadenylation, which normally occurs at the end of a gene's RNA transcript. The lack of U1 was causing the cleavage/polyadenylation machinery to kick into gear early.

The implication, Dreyfuss says, is that U1's normal role, in addition to splicing, is to keep the cleavage/polyadenylation machinery in check until the RNA polymerase enzyme that synthesizes the transcript reaches its finish line. The researchers propose a model in which U1 binds throughout the nascent RNA transcripts, stymieing the cleavage/polyadenylation machinery that tags along with the moving polymerase complex. This in turn protects the many potential polyadenylation signals encountered along the way, and could explain the relative abundance of U1 in cells compared to other snRNPs. The additional U1 corresponds to the greater amount needed for its additional function.

"The transcripts are under constant threat from the cleavage/polyadenylation machinery," Dreyfuss explains. "This machinery doesn't patiently wait for the transcript to reach the end of the gene; rather, the nascent RNA transcripts are subject to becoming attacked by this machinery. It's a constant danger they face, and the U1 snRNP suppresses it."

It is, he says, "a novel role" for U1, and a critical component for correctly making mRNA. "It is essential for the integrity of the transcriptome, the landscape of all mRNA molecules in the cell," he concludes.

Other coauthors on the paper include Penn researchers Daisuke Kaida, Michael Berg, Ihab Younis, Mumtaz Kasim, Larry Singh, and Lili Wan. The research was funded by the Association Française Contre les Myopathies and the Howard Hughes Medical Institute.

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $3.6 billion enterprise.

Penn’s School of Medicine is currently ranked #2 in U.S. News & World Report’s survey of research-oriented medical schools, and is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $367.2 million awarded in the 2008 fiscal year.

Penn Medicine’s patient care facilities include:

The Hospital of the University of Pennsylvania – the nation’s first teaching hospital, recognized as one of the nation’s top 10 hospitals by U.S. News & World Report.

Penn Presbyterian Medical Center – named one of the top 100 hospitals for cardiovascular care by Thomson Reuters for six years.

Pennsylvania Hospital – the nation’s first hospital, founded in 1751, nationally recognized for excellence in orthopaedics, obstetrics & gynecology, and psychiatry & behavioral health.

Additional patient care facilities and services include Penn Medicine at Rittenhouse, a Philadelphia campus offering inpatient rehabilitation and outpatient care in many specialties; as well as a primary care provider network; a faculty practice plan; home care and hospice services; and several multispecialty outpatient facilities across the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2009, Penn Medicine provided $733.5 million to benefit our community.

Karen Kreeger | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

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...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

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...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

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...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Ice shelf vibrations cause unusual waves in Antarctic atmosphere

25.10.2016 | Earth Sciences

Fluorescent holography: Upending the world of biological imaging

25.10.2016 | Power and Electrical Engineering

Etching Microstructures with Lasers

25.10.2016 | Process Engineering

More VideoLinks >>>