by: Jim Oldfield
Very small segments of genes called “microexons” influence how proteins interact with each other in the nervous system, say scientists at the University of Toronto.
It's a discovery that opens up a new line of research into the cause of autism.
The researchers found that microexons are used in neurons by alternative splicing, a process in which a single gene can produce many different proteins. Microexons are pasted – or spliced – into gene messengers known as mRNAs to generate forms of proteins that the nervous system needs to function properly.
The misregulation of this process, the researchers found, can have major effects on how proteins function.
“We’re seeing a new landscape of splicing regulation that is highly specific to the nervous system, and which is very important for controlling how proteins interact with each other,” said Benjamin Blencowe (pictured at right) a professor in U of T’s Donnelly Centre for Cellular and Biomolecular Research and department of molecular genetics.
“In addition, a large number of the microexons we detected show misregulation in people with autism.”
Until now, few microexons were known to exist. Scientists – including Blencowe and his colleagues at U of T – had previously created algorithms to predict which exons are spliced in mRNAs to produce proteins. But these algorithms failed to capture microexons.
In their new study, Blencowe and his colleagues, led by postdoctoral fellow Manuel Irimia, created a new computational tool that detects many more splicing combinations within a cell, including those that involve microexons. They used their tool to discover splicing of microexons in neurons.
Blencowe is cautiously optimistic about the potential therapeutic value of this discovery.
“While a lot more work has to be done to understand the functions of microexons in the nervous system, we were amazed by the extent to which microexons are misregulated in people with autism, which suggests they are an important component of this neurological disorder.”
Jim Oldfield is a writer with the Faculty of Medicine at the University of Toronto.