RELEVANCE: Researchers have known that mammalian microRNAs control protein production by causing the mRNAs to degrade, but they have wondered how much additional effects microRNAs impart by jamming the process that translates mRNAs into proteins. These results from a genome-wide study indicate that scientists can accurately study microRNA function and corresponding gene targets through examination of mRNA levels, which is easier than examining protein levels.
Short pieces of RNA, called microRNAs, control protein production by causing the proteins’ RNA templates (known as messenger RNA or mRNA) to be disabled by the cell, according to Whitehead Institute scientists.
Researchers have known that mammalian microRNAs control protein production by causing the mRNAs to degrade but they have wondered how much additional effects microRNAs impart by jamming the process that translates mRNAs into proteins.
For Whitehead Institute Member David Bartel, his lab’s genome-wide research helps answer this question and will serve as a foundation for future research.
“These results reveal the ultimate outcome of microRNA regulation of many genes and provide a framework for us to think about how microRNAs are acting,” says Bartel. “Also, we’re more confident that you can learn which genes are regulated by a microRNA simply by looking at the mRNA levels, which is much easier to do than looking at protein levels.”
This is the first time regulation of so many natural targets of microRNAs has been studied in such exacting detail. The Bartel lab’s results are published in Nature.
A cell uses each microRNA to dampen the protein production of hundreds of target mRNAs, thereby fine-tuning the cell’s protein output. To create a protein, a cell uses an RNA template that is copied from a gene. A cellular machine called a ribosome then translates this mRNA template into a chain of amino acids to form the protein. Until now, researchers were unsure where in this process microRNAs act—through elimination of mRNA targets or through interference with mRNA-to-amino acid translation without much change in the mRNA.
To date, some researchers have relied mostly on highly sensitive mRNA assays to study the effects of microRNAs. Because these assays measure only mRNA levels and not protein levels, researchers worried that any microRNA activity that reduced translation without reducing the mRNA would be missed, potentially skewing results.
To determine microRNAs’ effects on translation and mRNA levels, Huili Guo, a graduate student in the Bartel lab, performed genome-wide ribosome profiling of human and mouse cells. This test provides a snapshot of whether or not ribosomes are sitting on the mRNA templates. The presence of ribosomes on the mRNA indicates that the mRNA is being translated.
Guo then measured the levels of mRNAs in the cell. By accounting for the change in the amount of targeted mRNAs, she could derive the microRNAs’ effects at the translation level.
If microRNAs only disrupt translation, then targeted mRNA levels should be similar to those seen in controls. Also, the ribosome profile should show far fewer ribosomes on the targeted mRNAs as a result of interrupted translation. However, Guo found that the levels of the targeted mRNAs all decreased. Although the ribosome profiling indicated that translation was also slightly reduced on these mRNAs, the overall reduction in protein production was primarily due to the more greatly reduced mRNA levels.
To extend her results, Guo says other cells should be tested.
“I looked at cells that were growing under normal conditions,” says Guo. “But microRNAs have been linked to stress responses in some cells, so cells may act differently under those and other conditions.”
This research was supported by the National Institute of Health (NIH), the Agency for Science, Technology and Research, Singapore, the Ruth L. Kirschstein National Research Service Award, and the Howard Hughes Medical Institute (HHMI).
David Bartel is a Member at Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a Howard Hughes Medical Institute Investigator and a professor of biology at Massachusetts Institute of Technology.
“Mammalian microRNAs predominantly act to decrease target mRNA levels”
Nature, August 12, 2010
Huili Guo (1,2), Nicholas T. Ingolia (3,4), Jonathan S. Weissman (3,4), and David P. Bartel (1,2).
1. Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
2. Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
3. Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158, USA.
4. California Institute for Quantitative Biosciences, San Francisco, California 94158, USA.
Nicole Giese | Newswise Science News
The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie
How protein islands form
15.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
Researchers from the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science, the Italian Space Agency (ASI), and the Instituto Geofisico--Escuela Politecnica Nacional (IGEPN) of Ecuador, showed an increasing volcanic danger on Cotopaxi in Ecuador using a powerful technique known as Interferometric Synthetic Aperture Radar (InSAR).
The Andes region in which Cotopaxi volcano is located is known to contain some of the world's most serious volcanic hazard. A mid- to large-size eruption has...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
16.08.2017 | Physics and Astronomy
16.08.2017 | Materials Sciences
16.08.2017 | Interdisciplinary Research