Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study identifies molecular complex vital to creation of miRNAs

18.11.2004


Possible links to DiGeorge syndrome, schizophrenia also seen



Tiny bits of short-lived genetic material called microRNAs, or miRNAs, have attracted enormous interest from scientists since their discovery in humans only a few years ago. Viewed most broadly, they appear to play significant roles in controlling gene expression and development in many different settings.

Now, a new study from researchers at The Wistar Institute identifies for the first time a molecular complex vital for the creation of miRNAs. This complex, dubbed the microprocessor complex, contains two proteins, one of which has been linked to DiGeorge syndrome, the most common disorder of genetic deletion in humans. A swathe of DNA containing multiple genes is missing in DiGeorge syndrome patients, and many are born with heart defects, immune deficiencies, and developmental and behavioral problems. Intriguingly, one in four also goes on to develop schizophrenia, a disorder for which causative genes have yet to be identified. The new study appears in the November 11 issue of Nature.


"Discovery of this microprocessor complex gives us important insights into the processing mechanisms that generate miRNAs in the body," says Ramin Shiekhattar, Ph.D., an associate professor at Wistar and senior author on the Nature study. "At the same time, we see that one of the components of the complex is implicated in DiGeorge syndrome, suggesting that miRNA activity – or its lack – may be pivotal in the disease process of that multifaceted disorder."

The genes that code for miRNAs initially gives rise to a long primary RNA molecule that must first be cut into small precursor RNA molecules before final processing into mature miRNAs. The finished miRNAs are remarkably small, only 22 nucleotides in length, but powerful. These molecules appear to work by binding to complementary regions in messenger RNA, responsible for translating genes into proteins, or even to certain stretches of DNA. Either way, the result is gene silencing, which is one of the body’s main strategies for regulating genes.

The microprocessor complex discovered by Shiekhattar’s team is composed of two proteins called Drosha and DGCR8. Drosha had been previously identified as being involved in miRNA processing, but the role of DGCR8 is newly seen here. The Wistar scientists showed that both DGCR8 and Drosha were necessary for the processing of primary miRNA into a precursor miRNA – neither alone was sufficient to do the job. In another set of experiments, DGCR8 was intentionally inactivated, which led to excessive accumulations of the primary microRNA. DGCR8 is one of the several genes deleted in DiGeorge syndrome, and this link suggests several paths for future investigations. Shiekhattar plans, for example, to develop a strain of mice lacking the gene for DGCR8 to see whether they display any of the characteristics of DiGeorge syndrome. He also aims to study DiGeorge syndrome patients to see whether they exhibit the excessive accumulations of primary RNA that might be expected due to a DGCR8-deficient, and therefore nonfunctional, microprocessor complex.

Scientists have noted, too, that miRNAs are critical for proper neuronal development. Might miRNA activity, then, provide a new window on schizophrenia, at least in DiGeorge syndrome patients, but perhaps also more globally? "It would certainly be possible to look in schizophrenic populations for mutations in the DGCR8 gene," says Shiekhattar. "If those mutations were found, it could suggest of a significant role for miRNAs in schizophrenia." In the course of their study of the microprocessor complex, the Wistar scientists also identified a second and much larger molecular complex that also incorporates Drosha. This complex contains about 20 proteins, and another goal for Shiekhattar’s team in the future will be to ascertain the as-yet-unknown biological role of this complex.

The lead authors on the Nature study are Richard I. Gregory and Kai-ping Yan, with each contributing equally to the work. The remaining co-authors are Govindasamy Amuthan, Thimmaiah Chendrimada, Behzad Doratotaj, and Neil Cooch. Senior author Shiekhattar is an associate professor in two programs at Wistar, the gene expression and regulation program and molecular and cellular oncogenesis program. Support for the research was provided by the National Institutes of Health, the American Cancer Society, and the Jane Coffin Child Memorial Fund for Medical Research.

Franklin Hoke | EurekAlert!
Further information:
http://www.wistar.upenn.edu

More articles from Life Sciences:

nachricht Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

nachricht First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>