RNA Interference Decision-Making Processes On A Molecular Level

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RNA Interference Decision-Making Processes On A Molecular Level

http://www.medicalnewstoday.com/articles/76900.php

" How does RNAi work? " Researchers across the world have been trying

to answer this question for a number of years. Science has now come

closer to finding the answer thanks to a research group headed by

Prof. Renée Schroeder (MFPL) and Dr. ez (IMBA) based at

the Campus Vienna Biocenter. The group's results are being published

today in the internationally renowned scientific journal CELL and

underline the importance of Austrian RNA research, which is also

supported by the Austrian Science Fund FWF.

RNA interference (RNAi) is a natural cellular defence and regulation

mechanism which works by eliminating unwanted RNA molecules. Its

potential for use in therapy was officially recognised last year

with the presentation of the Nobel Prize in Physiology or Medicine.

Indeed, the first treatments to be based on this mechanism are

currently undergoing clinical testing. Nevertheless, the details of

this process still require a great deal of further research and

hence, offer potential for optimizing medical treatments based on

it.

No Risc. No Fun

It is precisely this potential that a group at the Campus Vienna

Biocenter recently tapped in order to clarify key details

surrounding the efficiency of RNA interference. Lead scientist Dr.

Stefan L. Ameres from the Max F. Perutz Laboratories (MFPL),

Department for Biochemistry at the University of Vienna, explains " A

key stage of RNA interference is the binding of the RNA that is to

be cleaved by RISC, the RNA-induced silencing complex. Already a lot

is known about the subsequent destruction of the target RNA by RISC,

but we have only little insight into the initial determination as to

which RNAs are bound and how exactly this happens. Working with the

Institute for Molecular Biotechnology of the Austrian Academy of

Sciences (IMBA), we have succeeded in making considerable progress

towards clarifying this process. "

The team initially focussed on characterising the influence of the

RNA structure. Variations of an RNA target molecule were created

where the RISC binding site became increasingly difficult to access

due to structural differences. Dr. Ameres comments on the findings

from the experiment: " The results were very clear indeed. The less

accessible the binding site, the less efficient the RISC-induced

elimination of the target RNA. Based on this data, we concluded that

RISC does not possess the means to change the structure of RNA

molecules an important finding towards the effective application of

RNAi. "

Another result was equally important to the understanding of RNA

interference. The strength of the interaction between target RNA and

RISC must exceed a certain threshold in order to trigger initiation

of the subsequent RNA elimination process. This result clearly

indicates that RISC binds RNA in a more or less random process and

that it is the strength of this bond that determines the subsequent

fate of the RNA. " One way of looking at this is that, while binding

its target RNA, RISC has to carry out a check to ensure that it is

only certain RNAs that are destroyed, " explains Dr. Ameres.