Featured Research

from universities, journals, and other organizations

A Kiss That Binds: Understanding The Interaction Of Fragile X Mental Retardation Protein And Kissing Complex RNAs

Date:
April 17, 2005
Source:
Cold Spring Harbor Laboratory
Summary:
Fragile X syndrome results from loss of expression of the Fragile X mental retardation protein (FMRP), the product of the FMR1 gene. Now, Drs. Robert and Jennifer Darnell and colleagues, from The Rockefeller University, report the uncovering of a new interaction between FMRP and messenger RNAs (mRNAs) containing a tertiary RNA structure termed a "kissing complex".

Fragile X syndrome is the most common inherited form of mental retardation, affecting approximately 1 in 3600 males and 1 in 4000-6000 females. Fragile X syndrome results from loss of expression of the Fragile X mental retardation protein (FMRP), the product of the FMR1 gene. Now, Drs. Robert and Jennifer Darnell and colleagues, from The Rockefeller University, report the uncovering of a new interaction between FMRP and messenger RNAs (mRNAs) containing a tertiary RNA structure termed a "kissing complex".

Related Articles


Their studies, published in the April 15th issue of Genes & Development, provide a new direction for efforts to understand how the loss of FMRP function leads to the complex behavioral and cognitive defects characteristic of Fragile X syndrome.

While the importance of identifying a function for FMRP has been clear for some time, what this function actually is has continued to evade researchers. FMRP is a protein characterized by the presence of three RNA binding domains: two tandem KH-type RNA binding domains and an RGG box. Scientists have focused on the identification of FMRP RNA ligands in an effort to understand FMRP function. This effort is particularly meaningful since FMRP is believed to regulate mRNA translation in the brain, and identifying the mRNA targets of this regulation would be a huge step in understanding how loss of this protein results in the varied and complex phenotypes of Fragile X syndrome.

In most Fragile X patients, loss of FMRP is due to silencing of FMR1 resulting from the unusual amplification of a CGG repeat (over 200 copies in affected patients versus less than 60 copies in unaffected individuals) that leads to hypermethylation of FMR1 and shut down of transcription of the gene. However, Fragile X patients expressing mutations or deletions within the FMR1 gene have also been described, including a severely affected patient harboring a missense mutation that resulted in a one amino acid change, isoleucine at position 304 for asparagine, in one of the KH domains of FMRP, KH2.

Dr. Darnell and colleagues focused on understanding how this specific mutation leads to loss of FMRP function. They first screened an RNA library to identify what RNA motif is recognized by the KH2 domain. They found that the KH2 domain of FMRP recognizes a loop-loop pseudoknot, or "kissing complex" structure in the RNA, and that this recognition is abrogated by the isoleucine to asparagine mutation. Notably, they show that the association of FMRP with the translation machinery (in brain polyribosomes) can be competed out with kissing complex RNA, an important finding since previous biochemical studies have reported altered polyribosome distribution of mRNAs in Fragile X patients.

These findings will redirect the search for the RNA targets of FMRP whose misregulation is responsible for the disease, to those containing kissing complex motifs.

Though much remains to be understood in the biology leading to Fragile X syndrome and the function of FMRP, Dr. Darnell is confident that "these findings may provide a crucial link between the association of FMRP in brain polyribosomes, its proposed role in regulation mRNA translation, and neurologic dysfunction in the Fragile X syndrome".


Story Source:

The above story is based on materials provided by Cold Spring Harbor Laboratory. Note: Materials may be edited for content and length.


Cite This Page:

Cold Spring Harbor Laboratory. "A Kiss That Binds: Understanding The Interaction Of Fragile X Mental Retardation Protein And Kissing Complex RNAs." ScienceDaily. ScienceDaily, 17 April 2005. <www.sciencedaily.com/releases/2005/04/050416183454.htm>.
Cold Spring Harbor Laboratory. (2005, April 17). A Kiss That Binds: Understanding The Interaction Of Fragile X Mental Retardation Protein And Kissing Complex RNAs. ScienceDaily. Retrieved November 27, 2014 from www.sciencedaily.com/releases/2005/04/050416183454.htm
Cold Spring Harbor Laboratory. "A Kiss That Binds: Understanding The Interaction Of Fragile X Mental Retardation Protein And Kissing Complex RNAs." ScienceDaily. www.sciencedaily.com/releases/2005/04/050416183454.htm (accessed November 27, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, November 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Experimental Ebola Vaccine Shows Promise In Human Trial

Experimental Ebola Vaccine Shows Promise In Human Trial

Newsy (Nov. 27, 2014) — A recent test of a prototype Ebola vaccine generated an immune response to the disease in subjects. Video provided by Newsy
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) — Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) — Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. 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

 

Health & Medicine

Mind & Brain

Living & Well

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