Featured Research

from universities, journals, and other organizations

Wiggly microRNA binding implies a more complex genome regulation

Date:
August 8, 2014
Source:
Thomas Jefferson University
Summary:
Non-standard microRNA silencing interactions appear more prevalent in human biology than previously believed, suggesting more complex roles for microRNAs, and helping explain why it's been difficult to translate microRNAs into human therapy. "The findings may help explain why the microRNA field has run into difficulty when translating these powerful molecules into therapies for diseases ranging from cancer to diabetes," explains the study's senior author.

MicroRNAs (miRNAs) regulate protein-coding gene abundance levels by interacting with the 3 end of various messenger RNAs. Each target site matches the first few nucleotides of the targeting miRNA, the so called "seed" region, and this interaction leads to the degradation of the target or prevents its translation into amino acids. This dogma has led researchers to largely look for perfect base-pair matching of the "seed" region among candidate targets.

Related Articles


New research published today (August 8th) in Nature's open access journal Scientific Reports suggests that non-canonical binding may be much more prevalent than previously expected, revealing a much broader array of targets for miRNAs that includes both regions that code for proteins and others that do not.

"The findings may help explain why the microRNA field has run into difficulty when translating these powerful molecules into therapies for diseases ranging from cancer to diabetes," says senior author Isidore Rigoutsos, Ph.D., Director of the Computational Medicine Center in the Sidney Kimmel Medical College at Thomas Jefferson University. "There is still so much we don't know about how miRNAs work in the body."

The research add to previous reports by the Jefferson group and by others demonstrating that the miRNA "targetome" -- the spectrum of RNAs that miRNAs attack -- is much more complex than previously anticipated. "Our study shows that even conserved miRNAs that we share with animals and insects can have very different behavior across organisms and even across different tissues in our bodies," says Rigoutsos.

For example, the team's analysis showed that one miRNA that's been implicated in cancer and is expressed by all vertebrates appears to bind to over 900 distinct sites in mouse embryonic stem cells, but does not bind to any sites in mouse brain cells, and only 25 sites in human pancreatic cells, suggesting that this one molecule likely has a variety of different and non-overlapping functions in mouse and human, and across different cell types.

Through an unbiased investigation of all possible combinations of miRNAs and experimentally-identified targets across seven tissue types and two organisms (human and mouse), the researchers found that the most likely pairings contained many instances of rogue binding in the seed region: instead of contiguous, well-formed base pairings, the nucleic acids of the seed region bulged and wobbled. In addition, the best target partners of miRNAs were often found in unexpected locations, such as in the 5 untranslated region of messenger RNAs transcripts or in RNA transcripts that do not code for proteins.

Given that most miRNA studied to date have focused on exploring perfect matches of the miRNA's seed region to the messenger RNAs' 3 untranslated regions, the abundance of alternatives binding sites suggests that many additional regulatory events may be at play in these previously unexplored areas. The apparent organism-dependence of these events may also help explain why studies showing effective miRNA approaches in animals do not translate so easily into humans. "If the repertoire of targets for one miRNA can be so different between cells of the same organism it is likely to also be different from one organism to the other," says Rigoutsos.


Story Source:

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


Journal Reference:

  1. Peter M. Clark, Phillipe Loher, Kevin Quann, Jonathan Brody, Eric R. Londin, Isidore Rigoutsos. Argonaute CLIP-Seq reveals miRNA targetome diversity across tissue types. Scientific Reports, 2014; 4 DOI: 10.1038/srep05947

Cite This Page:

Thomas Jefferson University. "Wiggly microRNA binding implies a more complex genome regulation." ScienceDaily. ScienceDaily, 8 August 2014. <www.sciencedaily.com/releases/2014/08/140808111925.htm>.
Thomas Jefferson University. (2014, August 8). Wiggly microRNA binding implies a more complex genome regulation. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2014/08/140808111925.htm
Thomas Jefferson University. "Wiggly microRNA binding implies a more complex genome regulation." ScienceDaily. www.sciencedaily.com/releases/2014/08/140808111925.htm (accessed December 21, 2014).

Share This


More From ScienceDaily



More Plants & Animals News

Sunday, December 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Monarch Butterflies Descend Upon Mexican Forest During Annual Migration

Monarch Butterflies Descend Upon Mexican Forest During Annual Migration

Reuters - Light News Video Online (Dec. 19, 2014) Millions of monarch butterflies begin to descend onto Mexico as part of their annual migration south. Rough Cut (no reporter narration) Video provided by Reuters
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
Powered by NewsLook.com
Birds Might Be Better Meteorologists Than Us

Birds Might Be Better Meteorologists Than Us

Newsy (Dec. 19, 2014) A new study suggests a certain type of bird was able to sense a tornado outbreak that moved through the U.S. a day before it hit. Video provided by Newsy
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:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

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