There are around 20,000 human genes that encode for protein, which carry out many of the essential functions of cells.
Scientists have now found that mRNAs have a previously unknown role in determining the shape of proteins.
This work showed that 3′UTR sequences help many regulatory proteins fold correctly.
The 3’UTR can hold onto these unstable, sticky regions so they do not affect protein folding, and ensure larger proteins fold correctly.
"RNA is an active participant in building proteins—providing guidance to ensure they fold correctly and can do their jobs properly," added Luo.
There are around 20,000 human genes that encode for protein, which carry out many of the essential functions of cells. Active genes are transcribed into molecules known as messenger RNAs (mRNAs), which are then translated by the cell into proteins. These proteins are composed of strings of amino acids that have to be properly folded into a specific three-dimensional shape to carry out their functions correctly. Scientists have now found that mRNAs have a previously unknown role in determining the shape of proteins. The findings have been reported in Cell.
This work focused on the end, or ‘tail’ of mRNA molecules, which seems ot help ensure that crucial proteins that perform regulatory functions are folded properly.
"The traditional view is that only specialized proteins act as chaperones to help other proteins fold correctly," explained Dr. Christine Mayr, MD, Ph.D., a member of the Sloan Kettering Institute at Memorial Sloan Kettering Cancer Center (MSK). "Our research shows that RNA can do this, too, and that mRNAs act as their own chaperones for a group of important, hard-to-fold proteins."
An mRNA molecule has a head region, a protein coding sequence, and a tail. "The head region is usually very small, so the coding sequence and the tail make up most of the RNA's total length," said Luo.
The tail is known as a 3'UTR, which does not encode for protein (UTR stands for untranslated region). It’s often been disregarded, but Mayr suspected it had importance, because these regions are found in so many species; this phenomenon is known as conservation.
This work showed that 3′UTR sequences help many regulatory proteins fold correctly.
Small proteins can often fold on their own without help, said Luo. But more complex proteins often carry sequences that are not stable enough to fold without assistance; these areas can link up with other sequences they are not supposed to, because they have a kind of ‘stickiness’ about them. This work found that over 2,700 genes have these challenging regions, and also carry conserved 3’UTRs. The 3’UTR can hold onto these unstable, sticky regions so they do not affect protein folding, and ensure larger proteins fold correctly.
"What we show is that for thousands of regulatory proteins in human cells, the genetic code alone isn't enough to make a functional protein; you need the RNA chaperone too," Mayr noted.
The study also highlights the vital roles of RNA. "RNA is an active participant in building proteins—providing guidance to ensure they fold correctly and can do their jobs properly," added Luo.
Sources: Memorial Sloan Kettering Cancer Center, Cell
