Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New study expands understanding of the role of RNA editing in gene control

27.12.2005


For many years, scientists thought gene activity was relatively straightforward: Genes were transcribed into messenger RNA, which was processed and translated into the proteins of the body. Certainly, there were many factors governing the transcription process, but gene control happened at the level of the DNA.



In the past few years, however, evidence for a more nuanced understanding of the total genetic system has steadily accumulated. Researchers at The Wistar Institute and elsewhere have been teasing out the details of a process called RNA editing, in which messenger RNA sequence is altered after transcription by editing enzymes, so that a single gene can produce a number of related but distinct variant proteins. Most recently, scientists have discovered an extensive family of small molecules called microRNAs, or miRNAs, that appear to target and inactivate particular messenger RNAs. This targeted gene silencing is now seen as one of the body’s primary strategies for regulating its genome.

Now, in a new study published online in Nature Structural & Molecular Biology, a Wistar-led team of scientists details the convergence of these two post-transcriptional genetic systems. The findings show that precursor miRNAs, like messenger RNAs, are themselves subject to specific RNA editing, the result of which is to suppress miRNA expression and its activity. The importance of understanding these joined processes can be seen in the fact that roles have been identified for miRNAs in embryonic development, cell and tissue differentiation, and, increasingly, in cancer formation.


"A couple of years ago, we started to investigate whether miRNA precursors were being edited in processing," says Kazuko Nishikura, Ph.D., senior author on the study and a professor in the gene expression and regulation program at The Wistar Institute. "We found that about half of all miRNA precursor molecules are subject to editing. Looking more closely at a particular miRNA precursor found in blood cells, we identified a specific site where editing leads to suppression of the mature miRNA."

Nishikura’s team demonstrated that two RNA editing enzymes known as ADAR1 and ADAR2, long the focus of study in her laboratory, are able to alter a specific occurrence of the nucleotide adenosine, changing it to inosine in the precursor molecule for miRNA-142, expressed in hematopoietic tissues. This editing had the effect of preventing a key miRNA processing enzyme called Drosha from cutting the precursor miRNA molecule at a critical step in that process.

Looking downstream along the miRNA processing pathway, the scientists also discovered that a molecular complex called RISC played a surprising role. Several components of RISC are known to be involved in normal miRNA processing. But the duties of an identified component of RISC called Tudor-SN were not known. In this study, Tudor-SN was found to be responsible for degrading miRNAs that had been edited in the earlier step, snipping into smaller bits the now useless precursor miRNA molecule precisely at the inosine site resulting from the earlier editing.

Taken together, the results of the study suggest that regulation of the genome is considerably more sophisticated than had been previously understood to be the case.

"People used to think that gene regulation was best done at the very beginning of the production line, which is transcription," says Nishikura. "Therefore, many scientists investigated transcription factors, activating proteins, and so on. But things have changed, and we now know that genes are controlled at many different levels."

The lead author on the Nature Structural & Molecular Biology study is Weidong Yang. Additional Wistar-based co-authors are Thimmaiah P. Chendrimada and Qingde Wang. Ramin Shiekhattar, Ph.D., a professor in two programs at Wistar, the gene expression and regulation program and molecular and cellular oncogenesis program, collaborated with senior author Nishikura on the investigation. (Shiekhattar’s own research has contributed to a better understanding of the processing steps that lead to mature miRNAs: See http://www.wistar.org/news_info/pressreleases/pr_11.03.05.htm.) The remaining coauthors on the current study are Miyoko Higuchi and Peter H. Seeburg at the Max Planck Institute for Medical Research in Heidelberg, Germany.

Marion Wyce | EurekAlert!
Further information:
http://www.wistar.org/news_info/pressreleases/pr_11.03.05.htm

More articles from Studies and Analyses:

nachricht Real-time feedback helps save energy and water
08.02.2017 | Otto-Friedrich-Universität Bamberg

nachricht The Great Unknown: Risk-Taking Behavior in Adolescents
19.01.2017 | Max-Planck-Institut für Bildungsforschung

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>