Some 'Junk' DNA Is Important Guide For Nerve-cell Channel Production

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Some 'Junk' DNA Is Important Guide For Nerve-cell Channel Production

http://www.sciencedaily.com/releases/2008/02/080205115800.htm

Researchers at the University of Pennsylvania School of Medicine have

discovered that introns, or junk DNA to some, associated with RNA are

an important molecular guide to making nerve-cell electrical

channels. In nerve cells, some ion channels are located in the

dendrite, which branch from the cell body of the neuron. Dendrites

detect the electrical and chemical signals transmitted to the neuron

by the axons of other neurons. Abnormalities in the dendrite

electrical channel are involved in epilepsy, neurodegenerative

diseases, and cognitive disorders, among others.

Introns are commonly looked on as sequences of " junk " DNA found in

the middle of gene sequences, which after being made in RNA are

simply excised in the nucleus before the messenger RNA is transported

to the cytoplasm and translated into a protein. In 2005, the Penn

group first found that dendrites have the capacity to splice

messenger RNA, a process once believed to only take place in the

nucleus of cells.

Now, in the current study, the group has found that an RNA encoding

for a nerve-cell electrical channel, called the BK channel, contains

an intron that is present outside the nucleus. This intron plays an

important role in ensuring that functional BK channels are made in

the appropriate place in the cell.

Senior author Eberwine, PhD, Elmer Bobst Professor of

Pharmacology, and lead authors Miyashiro, and J. Bell,

PhD, both in Eberwine's lab, report their findings in the early

online edition of the Proceedings of the National Academy of Sciences

February 4.

When this intron-containing RNA was knocked out, leaving the maturely

spliced RNA in the cell, the electrical properties of the cell became

abnormal. " We think the intron-containing mRNA is targeted to the

dendrite where it is spliced into the channel protein and inserted

locally into the region of the dendrite called the dendritic spine.

The dendritic spine is where a majority of axons from other cells

touch a particular neuron to facilitate neuronal communication " says

Eberwine. " This is the first evidence that an intron-containing RNA

outside of the nucleus serves a critical cellular function. "

" The intron acts like a guide or gatekeeper, " says Eberwine. " It keys

the messenger RNA to the dendrite for local control of gene

expression and final removal of the intron before the channel protein

is made. Just because the intron is not in the final channel protein

doesn't mean that it doesn't have an important purpose. "

The group surmises that the intron may control how many mRNAs are

brought to the dendrite and translated into functional channel

proteins. The correct number of channels is just as important for

electrical impulses as having a properly formed channel.

The investigators believe that this is a general mechanism for the

regulation of cytoplasmic RNAs in neurons. Given the central role of

dendrites in various physiological functions they hope to relate this

new knowledge to understanding the molecular underpinnings of memory

and learning, as well as components of cognitive dysfunction

resulting from neurological disease.

Co-authors are Jai-Yoon Sul, T. Buckley, Jeanine Jochems,

F. Meaney, Phil Haydon, and D. Parsons, all from Penn, as well

as Cantor from Sequenom Inc. (San Diego) and

McCullough from Boston University.

This work was funded by the National Institute of Mental Health, the

National Institute of Child Health and Human Development, the

National Institute on Aging and the Health Research Funds of the

State of Pennsylvania.