Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Some long non-coding RNAs are conventional after all

07.04.2014

Not so long ago researchers thought that RNAs came in two types: coding RNAs that make proteins and non-coding RNAs that have structural roles.

Then came the discovery of small RNAs that opened up whole new areas of research. Now researchers have come full circle and predicted that some long non-coding RNAs can give rise to small proteins that have biological functions. A recent study in The EMBO Journal describes how researchers have used ribosome profiling to identify several hundred long non-coding RNAs that may give rise to small peptides.


Some long non-coding RNAs are conventional after all

“We have identified hundreds of open reading frames in the long non-coding RNAs of humans and zebrafish that may give rise to functional proteins using ribosome profiling,” says Antonio Giraldez, one of the lead authors of the study and a professor at Yale University School of Medicine in the United States.

Ribosome profiling allows scientists to measure how much RNA is translated into protein. The method allows direct quantification of the messenger RNA fragments protected by the ribosome after digestion with the enzyme nuclease. The nucleases destroy the bonds between the exposed nucleotides that make up RNA and which are not protected by the protein-making machinery of the ribosome. What is left behind is a measurable amount of RNA destined to produce protein.

The researchers were able to visualize translation and the movement of the ribosome every three nucleotides, which corresponds to the size of each codon on the RNA producing an amino acid. This was possible by combining the high resolution of ribosome profiling with a bioinformatic tool developed in the Giraldez laboratory called ORFScore.

“Crucial to our study was the parallel use of a second computational method that relies on a bioinformatic tool called micPDP,” says Giraldez. “micPDP revealed that the RNAs identified by ribosome profiling correspond to peptides that have been conserved over the course of evolution. This strongly suggests that these genes encode proteins that have specific functions in these animals.”

As a further validation of their method, the scientists went one step further and used mass spectrometry to detect and characterize almost 100 of the peptides coded by the RNAs.

Until recently, long non-coding RNAs were thought to be restricted to the more mundane but nonetheless important structural roles that are essential to support the function of the cell. “We think the main reason that these small functional peptides have been missed in earlier studies is due to the assumptions that have to be made when assigning functions to large numbers of genes,” says EMBO Member Nikolaus Rajewsky, Professor at the Max-Delbrück-Center in Berlin, Germany, Director of the Berlin Institute for Medical Systems Biology and one of the lead authors whose team contributed the micPDP computational method to identify conserved micropeptides. “Short open reading frames are so numerous that by design standard genome annotation methods have to filter out short open reading frames.”

There are many short peptides in nature, for example neuropeptides or insulin, but unlike the small peptides arising from long non-coding RNAs they are produced as larger preproteins that need to be trimmed to their final size. The first reports of activities for the small peptides produced by long non-coding RNAs have already begun to emerge. Schier and colleagues recently reported in Science1 a small peptide that functions as a signal to promote cell motility in the early fish embryo. The aptly named Toddler protein arises from long non-coding RNAs and acts as an activator of a G protein coupled receptor, one of the essential signaling molecules in the cell. Earlier work showed that a long non-coding RNA produced by the tarsal-less/polished rice/mille-pattes gene encodes small peptides that control epithelial morphogenesis in Drosophila and the flour beetle Tribolium.

“Our identification of hundreds of translated small open reading frames significantly expands the set of micropeptide-encoding vertebrate genes providing an entry point to investigate their real life functions,” says Giraldez.

“The peptide predictions reported in these studies are tantalizing, but this is just the first step. Things should get really interesting as the community explores the functions of the predicted peptides in vivo,” says Stephen M. Cohen, Professor at the Institute of Molecular and Cell Biology in Singapore who is not an author of the paper. “I imagine that we’ll be hearing a lot about this new peptide world in the years to come.”
Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation

Ariel A. Bazzini, Timothy G. Johnstone, Romain Christiano, Sebastian D.
Mackowiak, Benedikt Obermayer, Elizabeth S. Fleming,Charles E. Vejnar, Miler T. Lee, Nikolaus Rajewsky, Tobias C. Walther and Antonio J. Giraldez

Read the paper:
doi: 10.1002/embj.201488411

http://emboj.embopress.org/content/early/2014/04/04/embj.201488411

1 Toddler: An Embryonic Signal That Promotes Cell Movement via Apelin Receptors (2014) Pauli et al. Science 14 February 2014: 343 doi:10.1126/science.1248636

Further information on The EMBO Journal is available at emboj.embopress.org

Media Contacts

Barry Whyte
Head | Public Relations and Communications
barry.whyte@embo.org

Thomas Schwarz-Romand
Senior Editor, The EMBO Journal
Tel: +49 6221 8891 407
schwarzr@embo.org

About EMBO
EMBO is an organization of more than 1500 leading researchers that promotes excellence in the life sciences. The major goals of the organization are to support talented researchers at all stages of their careers, stimulate the exchange of scientific information, and help build a European research environment where scientists can achieve their best work.

EMBO helps young scientists to advance their research, promote their international reputations and ensure their mobility. Courses, workshops, conferences and scientific journals disseminate the latest research and offer training in techniques to maintain high standards of excellence in research practice. EMBO helps to shape science and research policy by seeking input and feedback from our community and by following closely the trends in science in Europe.
For more information: www.embo.org

Yvonne Kaul | EMBO

Further reports about: EMBO RNA RNAs conventional genes identified non-coding nucleotides peptides profiling proteins ribosome rise small

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

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...

Im Focus: Quantum Particles Form Droplets

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...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

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,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

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

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>