PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Non-coding antisense RNA can be used to stimulate protein production

Non-coding antisense RNA can be used to stimulate protein production
2012-10-16
(Press-News.org) While studying Parkinson's disease, an international research group made a discovery which can improve industrial protein synthesis for therapeutic use. They managed to understand a novel function of non-protein coding RNA: the protein synthesis activity of coding genes can be enhanced by the activity of the non-coding one called "antisense."

To synthesize proteins, the DNA needs RNA molecules serving as short "transcriptions" of the genetic information. The set of all these RNA molecules is called "transcriptome." In the human transcriptome, along with around 25 thousand sequences of coding RNA (i.e. the sequences involved in the synthesis process), an even larger number of non-coding RNA sequences can be found. Some of these RNAs are called "antisense" because they are complementary to sequences of coding RNA called "sense" (the pairing of a sense and an antisense RNA can be seen as a zip).

The RIKEN Omics Science Center has previously discovered that many of the protein coding genes have corresponding antisense RNAs. A study published in Nature, coordinated by a group of SISSA researchers in Trieste, Italy, has now found that a particular type of antisense RNAs stimulate the translation of the protein coding mRNAs that they overlap to. This is in sharp contrast with the current belief that antisense RNAs are universally associated to negative regulation of protein translation.

Most of the mammalian genome is transcribed producing non-coding RNA. The RIKEN FANTOM projects have earlier demonstrated that the largest output of the genome is constituted by non-coding RNAs. More than 70% of the mRNAs are associated in cells with non-coding antisense RNAs, which are usually thought to negatively repress transcription or translation.

In an exceptional collaborative study based on RIKEN FANTOM sense-antisense cDNA clones, the consortium (including SISSA and the RIKEN Omics Science Center) has found a class of non-coding antisense RNAs that do the contrary of what is currently known: enhance translation of mRNAs with which they are pairing. The researchers identified this function studying the antisense of the mRNA of Uchl1, a mouse gene involved in brain function and neurodegenerative diseases. The team, using bioinformatics and data-mining at RIKEN, has also discovered that the antisense of Uchl1 RNA is not a single case but instead is the representative of a larger class of mammalian antisense RNAs, which function is to increase translation. This is the first report of an antisense RNA that increases protein production, which works both in mouse and human cells and is predicted to have similar function in other organisms.

The mechanism to stimulate translation is based on increased association of mRNAs with ribosomes, which is mediated by a SINEB2 element, a repetitive sequence in the antisense of Uchl1 RNA, which is placed in an inverted orientation in the non-coding RNA. The specificity is given by a short antisense RNA sequence that hybridizes with the initial part of the protein encoding mRNA.

Why is it an important discovery?

Very little used to be known about "long, non-coding" RNAs and this new research sheds light on some of these molecules. "We focused on one gene, Uchl1, whose mutations are linked to some hereditary types of Parkinson's disease," stated Stefano Gustincich, Professor at SISSA. "We have seen that the non-coding antisense RNA matched to this gene is made up of two fragments, the real antisense fragment matching with the sense RNA that codifies the protein and the SineB2 sequence. The antisense fragment has the function of a 'lock' into which the key of the coding RNA specific for that gene is inserted, while the other one has a stimulating function on protein synthesis."

If you change the antisense fragment with the analogous of another gene, the SineB2 sequence maintains its stimulating function on the new gene. "This is important," explained Gustincich "because it means that the action of sineB2 could be used to stimulate protein production for therapeutic use – any protein – in industrial synthesis processes."

"We are delighted to see that there is one more function for long non-coding RNAs," says Piero Carninci, Team Leader at RIKEN OSC. "Since the initial discovery that the majority of the genome produces so many non-coding RNAs, there has been a general skepticism related to the possible function of these RNAs. This is a milestone study identifying a novel class of non-coding RNAs which have a key regulatory function, enhancing protein translation. Additionally, this function is mediated by repetitive elements, so far generally considered the 'junk' fraction of the genome, suggesting that the concept that most of the genome is 'junk' should be revisited. After all, there may be function embedded in any part of the genome, which we do not yet understand."

RIKEN and the RIKEN venture company TransSINE Technologies are committed to exploit commercial applications of this specific structure of the antisense RNA.

These RNAs, called SINEUPs, can be engineered to stimulate translation of other proteins, by changing the overlapping antisense region to target any protein of industrial or therapeutic interest. Initial target proteins will include therapeutic proteins, like antibodies or other soluble factors, as well as other basic studies to understand gene function by overexpression of proteins. RIKEN believes that this work can be broadly used.



INFORMATION:

Reference

Claudia Carrieri, Marta Biagioli, Laura Cimatti, Anne Beugnet, Isidre Ferrer, Silvia Zucchelli, Stefano Biffo, Allistar Forrest, Piero Carninci, Elia Stupka, and Stefano Gustincich. "Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat." Nature, 2012, DOI: 10.1038/nature11508

About RIKEN

RIKEN is Japan's flagship research institute devoted to basic and applied research. Over 2500 papers by RIKEN researchers are published every year in reputable scientific and technical journals, covering topics ranging across a broad spectrum of disciplines including physics, chemistry, biology, medical science and engineering. RIKEN's advanced research environment and strong emphasis on interdisciplinary collaboration has earned itself an unparalleled reputation for scientific excellence in Japan and around the world.

About the RIKEN Omics Science Center (OSC)

Omics is the comprehensive study of molecules in living organisms. The complete sequencing of genomes (the complete set of genes in an organism) has enabled rapid developments in the collection and analysis of various types of comprehensive molecular data such as transcriptomes (the complete set of gene expression data) and proteomes (the complete set of intracellular proteins). Fundamental omics research aims to link these omics data to molecular networks and pathways in order to advance the understanding of biological phenomena as systems at the molecular level.

Here at the RIKEN Omics Science Center, we are developing a versatile analysis system, called the "Life Science Accelerator (LSA)," with the objective of advancing omics research. LSA is a multi-purpose, large-scale analysis system that rapidly analyzes molecular networks. It collects various genome-wide data at high throughput from cells and other biological materials, comprehensively analyzes experimental data, and thereby aims to elucidate the molecular networks of the sample. The term "accelerator" was chosen to emphasize the strong supporting role that this system will play in supporting and accelerating life science research worldwide.

Reach us on Twitter: @rikenresearch


[Attachments] See images for this press release:
Non-coding antisense RNA can be used to stimulate protein production

ELSE PRESS RELEASES FROM THIS DATE:

Genetic protection against arsenic

2012-10-16
Evolution has not only controlled human development over millions of years, it also has an impact on modern man. This is one of the conclusions of a study of Argentinian villagers in the Andes, where the water contains high levels of arsenic. A gene variant that produces efficient and less toxic metabolism of arsenic in the body was much more common among the villagers than among other indigenous groups in South or Central America. The study was a collaborative effort by Karin Broberg from Lund University and Carina Schlebusch and Mattias Jakobsson from Uppsala University ...

Dark matter filament studied in 3-D for the first time

2012-10-16
Astronomers using the NASA/ESA Hubble Space Telescope have studied a giant filament of dark matter in 3D for the first time. Extending 60 million light-years from one of the most massive galaxy clusters known, the filament is part of the cosmic web that constitutes the large-scale structure of the Universe, and is a leftover of the very first moments after the Big Bang. If the high mass measured for the filament is representative of the rest of the Universe, then these structures may contain more than half of all the mass in the Universe. The theory of the Big Bang predicts ...

The sound in Saturn's rings: RUB-Physicists explain nonlinear dust acoustic waves in dusty plasmas

2012-10-16
Dusty plasmas can be found in many places both in space and in the laboratory. Due to their special properties, dust acoustic waves can propagate inside these plasmas like sound waves in air, and can be studied with the naked eye or with standard video cameras. The RUB physicists Prof. Dr. Dr. h.c. Padma Kant Shukla and Dr. Bengt Eliasson from the Faculty of Physics and Astronomy have published a model with which they describe how large amplitude dust acoustic waves in dusty plasmas behave. The researchers report their new findings in the journal Physical Review E. Different ...

Novel discovery links anti-cancer drugs to muscle repair

2012-10-16
OTTAWA, October 16, 2012 – Few drugs are available to treat muscle injury, muscle wasting and genetic disorders causing muscle degeneration, such as Duchenne muscular dystrophy. A compelling discovery that may change this was made recently by a research group led by Dr. Robert Korneluk, distinguished professor at University of Ottawa's Faculty of Medicine and founder of the CHEO Research Institute's Apoptosis Research Centre, was reported today in Science Signaling. "We know of five pharmaceutical companies pursuing phase one clinical trials with specific drugs to treat ...

Pollenizer research should help seedless watermelon farmers

Pollenizer research should help seedless watermelon farmers
2012-10-16
Research from North Carolina State University on flower production and disease resistance in watermelon varieties should help bolster seedless watermelon harvests for farmers. Seedless watermelons are more popular than seeded watermelons, making them a more profitable crop for farmers. But the flowers of seedless watermelon plants must be fertilized with pollen from the male flowers of seeded watermelon plants, because seedless plants do not produce genetically viable pollen. This is a problem, because seeded watermelon plants take up space, nutrients and water that ...

A change of strategy is needed to save the Sumatran orangutans

A change of strategy is needed to save the Sumatran orangutans
2012-10-16
This press release is available in German. Orangutans are the only large apes in Asia and mainly live in trees. Today, the population only includes two species: While the Borneo orangutan populates large sections of the Southeast Asian island of Borneo, nowadays the Sumatran orangutan is only found at the northern tip of the island of Sumatra. With a current population of only around 6,600 Sumatra orangutans, a figure which is dropping rapidly and constantly, this species is on the Red List of Threatened Species. When large areas of rainforest were cleared in Sumatra ...

Less-invasive method of brain stimulation helps patients with Parkinson's disease

2012-10-16
Philadelphia, Pa. (October 16, 2012) – Electrical stimulation using extradural electrodes—placed underneath the skull but not implanted in the brain—is a safe approach with meaningful benefits for patients with Parkinson's disease, reports the October issue of Neurosurgery, official journal of the Congress of Neurological Surgeons. The journal is published by Lippincott Williams & Wilkins, a part ofWolters Kluwer Health. The technique, called extradural motor cortex stimulation (EMCS), may provide a less-invasive alternative to electrical deep brain stimulation (DBS) ...

Stat5 predicts outcomes for prostate cancer patients after radical prostatectomy

Stat5 predicts outcomes for prostate cancer patients after radical prostatectomy
2012-10-16
PHILADELPHIA—Men who had high levels of the activated Stat5 protein in their prostate cancer after a radical prostatectomy were more likely to have a recurrence or die from the disease compared to men who had little to no presence of the growth protein, according to a recent study published in Human Pathology by Jefferson's Kimmel Cancer Center researchers. This suggests, Stat5, a protein that when activated signals cancer cells to grow and survive, could be an ideal biomarker to help guide patients and physicians for future treatment. The research team, led by ...

Presidential candidate body language plays little role in voter perception

2012-10-16
Washington, DC (October 16, 2012) Viewer impressions of political candidates are heavily weighted to the content of their speech rather than the body language, a new study published in the Journal of Communication has found. The research, conducted by a trio of German scholars, presents a shift from past research showing that nonverbal communication plays a larger role than verbal in presidential debates. Marcus Maurer (Friedrich-Schiller-Universitaet), Friederike Nagel (Johannes Gutenberg-Universitaet), and CarstenReinemann (Ludwig Maxillians-Universitaet) conducted ...

Eating lots of carbs, sugar may raise risk of cognitive impairment, Mayo Clinic study finds

2012-10-16
ROCHESTER, Minn. -- People 70 and older who eat food high in carbohydrates have nearly four times the risk of developing mild cognitive impairment, and the danger also rises with a diet heavy in sugar, Mayo Clinic researchers have found. Those who consume a lot of protein and fat relative to carbohydrates are less likely to become cognitively impaired, the study found. The findings are published in the Journal of Alzheimer's Disease. The research highlights the importance of a well-rounded diet, says lead author Rosebud Roberts, M.B., Ch.B., a Mayo Clinic epidemiologist. "We ...

LAST 30 PRESS RELEASES:

New superconductor with hallmark of unconventional superconductivity discovered

Global HIV study finds that cardiovascular risk models underestimate for key populations

New study offers insights into how populations conform or go against the crowd

Development of a high-performance AI device utilizing ion-controlled spin wave interference in magnetic materials

WashU researchers map individual brain dynamics

Technology for oxidizing atmospheric methane won’t help the climate

US Department of Energy announces Early Career Research Program for FY 2025

PECASE winners: 3 UVA engineering professors receive presidential early career awards

‘Turn on the lights’: DAVD display helps navy divers navigate undersea conditions

MSU researcher’s breakthrough model sheds light on solar storms and space weather

Nebraska psychology professor recognized with Presidential Early Career Award

New data shows how ‘rage giving’ boosted immigrant-serving nonprofits during the first Trump Administration

Unique characteristics of a rare liver cancer identified as clinical trial of new treatment begins

From lab to field: CABBI pipeline delivers oil-rich sorghum

Stem cell therapy jumpstarts brain recovery after stroke

Polymer editing can upcycle waste into higher-performance plastics

Research on past hurricanes aims to reduce future risk

UT Health San Antonio, UTSA researchers receive prestigious 2025 Hill Prizes for medicine and technology

Panorama of our nearest galactic neighbor unveils hundreds of millions of stars

A chain reaction: HIV vaccines can lead to antibodies against antibodies

Bacteria in polymers form cables that grow into living gels

Rotavirus protein NSP4 manipulates gastrointestinal disease severity

‘Ding-dong:’ A study finds specific neurons with an immune doorbell

A major advance in biology combines DNA and RNA and could revolutionize cancer treatments

Neutrophil elastase as a predictor of delivery in pregnant women with preterm labor

NIH to lead implementation of National Plan to End Parkinson’s Act

Growth of private equity and hospital consolidation in primary care and price implications

Online advertising of compounded glucagon-like peptide-1 receptor agonists

Health care utilization and costs for older adults aging into Medicare after the affordable care act

Reading the genome and understanding evolution: Symbioses and gene transfer in leaf beetles

[Press-News.org] Non-coding antisense RNA can be used to stimulate protein production