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 Smart Data Transformation – Surfing the Big Wave
02.12.2016 | Fraunhofer-Institut für Angewandte Informationstechnik FIT

nachricht Climate change could outpace EPA Lake Champlain protections
18.11.2016 | University of Vermont

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: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

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...

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

IHP presents the fastest silicon-based transistor in the world

05.12.2016 | Power and Electrical Engineering

InLight study: insights into chemical processes using light

05.12.2016 | Materials Sciences

High-precision magnetic field sensing

05.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>