Featured Research

from universities, journals, and other organizations

Genome-wide Map Shows Precisely Where MicroRNAs Do Their Work

Date:
July 6, 2009
Source:
Rockefeller University
Summary:
MicroRNAs are the newest kid on the genetic block. By regulating the unzipping of genetic information, these tiny molecules have set the scientific world alight with such wide-ranging applications as onions that can't make you cry and therapeutic potential for new treatments for viral infections, cancer and degenerative diseases. But the question remains: How do they work?

Three's a crowd. By using a technique that molecularly cements the protein Argonaute (gray) to messenger RNA (blue), scientists have mapped the precise location of microRNAs (red) across the mouse genome. Understanding where microRNAs bind could help scientists devise ways of turning off problematic genes such as those linked to cancer.
Credit: Image courtesy of Rockefeller University

MicroRNAs are the newest kid on the genetic block. By regulating the unzipping of genetic information, these tiny molecules have set the scientific world alight with such wide-ranging applications as onions that can’t make you cry and therapeutic potential for new treatments for viral infections, cancer and degenerative diseases. But the question remains: How do they work?

In research to appear in the June 17 advance online issue of Nature, Robert B. Darnell, head of the Laboratory of Molecular Neuro-oncology, and his team at Rockefeller University provide a long-awaited key clue to answering that question. By using a technique that molecularly cements proteins to RNAs, the team has decoded a map of microRNA-messenger RNA interactions in the brain, an advance that holds promise for biology and human disease, for example by silencing trouble-making genes linked to disease.

MicroRNAs rewrote the rules of gene expression in 2001 when they were found to bind to messenger RNA and shut down protein production, a process called RNA interference. By 2006, when the Nobel Prize in medicine was given for the discovery of RNA interference, scientists around the globe had even narrowed down microRNAs’ primary site of action to somewhere around the end of the RNA transcript. What scientists couldn’t nail down was the exact string of nucleotides to which the microRNAs bind along a messenger RNA transcript.

“To understand exactly how microRNAs work, you want to know their precise targets,” says Darnell, who is a Howard Hughes Medical Institute investigator

and Robert and Harriet Heilbrunn Professor at Rockefeller. “You want a map that tells you which messenger RNAs each microRNA targets and exactly where they are binding.”

The problem was that on any given messenger RNA, there are many sites to which a single microRNA can theoretically bind, and there are hundreds of microRNAs in every cell. Prior techniques — primarily relying on computer predictions — weren’t very good at sorting through the morass of predictions to identify the real sites, explains Darnell. The trick to getting such a map was to freeze a snapshot of microRNAs directly bound to messenger RNA in living cells. Working specifically in mouse brain tissue, that’s what Darnell and his team did using a technique the lab developed called high throughput sequence-crosslinking immunoprecipitation, or HITS-CLIP.

In order to shut down a gene before it is translated, microRNAs must be guided to their target messenger RNAs via a protein called Argonaute. The Argonaute-microRNA-messenger RNA complex now forms a sandwich structure where the microRNA is compressed in the middle. By using their technique to fuse Argonaute to these two RNAs, the team was then able to identify the bound microRNA and its precise target sites across all messenger RNAs expressed in the mouse brain.

The researchers, including first author Sung-Wook Chi, a graduate fellow in the Tri-Institutional Computational Biology Program, Julie Zang, a biomedical fellow, and Aldo Mele, a research assistant, found that on average, about two microRNAs bind to each messenger RNA. They also found that microRNAs bind to nucleotides not only at the terminal end of a messenger RNA, but also at other regions including sequences coding for proteins and sequences once thought to be “junk RNA,” providing new insights into microRNA biology.

“It is thought that RNA is the molecule that can explain the gap between the complexity of cellular functions and our limited number of genes,” says Darnell. “We now have a platform to evaluate the degree to which microRNAs contribute to this complexity with an extraordinary amount of precision.”


Story Source:

The above story is based on materials provided by Rockefeller University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Chi et al. Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature, June 18, 2009; DOI: 10.1038/nature08170

Cite This Page:

Rockefeller University. "Genome-wide Map Shows Precisely Where MicroRNAs Do Their Work." ScienceDaily. ScienceDaily, 6 July 2009. <www.sciencedaily.com/releases/2009/06/090618190622.htm>.
Rockefeller University. (2009, July 6). Genome-wide Map Shows Precisely Where MicroRNAs Do Their Work. ScienceDaily. Retrieved July 30, 2014 from www.sciencedaily.com/releases/2009/06/090618190622.htm
Rockefeller University. "Genome-wide Map Shows Precisely Where MicroRNAs Do Their Work." ScienceDaily. www.sciencedaily.com/releases/2009/06/090618190622.htm (accessed July 30, 2014).

Share This




More Plants & Animals News

Wednesday, July 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Raw: Thousands Flocking to German Crop Circle

Raw: Thousands Flocking to German Crop Circle

AP (July 30, 2014) Thousands of people are trekking to a Bavarian farmer's field to check out a mysterious set of crop circles. (July 30) Video provided by AP
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Raw: Otters Enjoy Water Slides at Japan Zoo

Raw: Otters Enjoy Water Slides at Japan Zoo

AP (July 30, 2014) River otters were hitting the water slides to beat the summer heatwave on Wednesday at Ichikawa City's Zoological and Botanical Garden. (July 30) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News



      Save/Print:
      Share:

      Free Subscriptions


      Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

      Get Social & Mobile


      Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

      Have Feedback?


      Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
      Mobile: iPhone Android Web
      Follow: Facebook Twitter Google+
      Subscribe: RSS Feeds Email Newsletters
      Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins