Non-coding antisense RNA can be used to stimulate protein production
SINEUPs are non-coding antisense RNAs, containing SINEB2 element, which can be used to target protein coding RNAs and stimulate protein production. By changing the "target antisense sequence" region, any mRNA ("your gene") can be targeted to stimulate protein production, mediated by the "protein synthesis activation domain." Credit: RIKEN
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.
More information: 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
Journal reference: Nature
Provided by RIKEN
- Scientists discover role for dueling RNAs Nov 16, 2006 | not rated yet | 0
- Scientists find genetic oddity protects sex cells Nov 22, 2006 | not rated yet | 0
- Non-coding RNA has role in inherited neurological disorder -- and maybe other brain diseases too Jun 21, 2011 | not rated yet | 0
- Human cells can copy not only DNA, but also RNA Aug 10, 2010 | not rated yet | 0
- Newly discovered gene plays vital role in cancer Feb 27, 2009 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
University of Minnesota Medical School researchers from the Masonic Cancer Center, University of Minnesota, in partnership with the University's Brain Tumor Program, have developed a new mouse model of malignant peripheral ...
Genetics 16 hours ago | 5 / 5 (1) | 0 |
Northwestern University scientists have shown a gene involved in neurodegenerative disease also plays a critical role in the proper function of the circadian clock.
Genetics May 16, 2013 | 3 / 5 (1) | 1 |
Informed consent is the backbone of patient care. Genetic testing has long required patient consent and patients have had a "right not to know" the results. However, as 21st century medicine now begins to use the tools of ...
Genetics May 16, 2013 | 5 / 5 (1) | 3 |
Ethicists provide framework supporting new recommendations on reporting incidental findings in gene sequencing
In a paper published in Science Express, a group of experts led by bioethicists in the Center for Medical Ethics and Health Policy at Baylor College of Medicine provide a framework for the new American College of Medical Geneti ...
Genetics May 16, 2013 | not rated yet | 0
The use of genome-wide analysis (GWA), where the entirety of an individual's DNA is examined to look for the genomic mutations or variants which can cause health problems is a massively useful technology for diagnosing disease. ...
Genetics May 16, 2013 | not rated yet | 0
In a remote fishing community in Venezuela, a lone fisherman sits on a cliff overlooking the southern Caribbean Sea. This man –– the lookout –– is responsible for directing his comrades on the water, ...
43 minutes ago | not rated yet | 0 |
A novel approach to obstructing the runaway inflammatory response implicated in some types of asthma has shown promise in a Phase IIa clinical trial, according to U. S. researchers.
37 minutes ago | not rated yet | 0
Authorities are investigating rice mills in southern China following tests that found almost half of the staple grain in one of the country's largest cities was contaminated with a toxic metal.
43 minutes ago | not rated yet | 0
Scientists from Nanyang Technological University (NTU) and Lund University, Sweden, have bioengineered a novel molecule which has been proven to successfully kill tumour cells.
52 minutes ago | not rated yet | 0
Clinical measurement of physical activity appears to be an independent predictor of whether or not patients with chronic obstructive pulmonary disease (COPD) will end up being hospitalized, according to a new study conducted ...
22 minutes ago | not rated yet | 0
Delayed transfer to the intensive care unit (ICU) in hospitalized patients significantly increases the risk of dying in the hospital, according to a new study from researchers in Chicago.
2 minutes ago | not rated yet | 0