For people who know about RNA mostly from its place in the central dogma of biology — DNA ➙ RNA ➙ Protein — this story may hold a number of surprises.
That handy equation, taught in Biology 101 courses around the globe, sums up the flow of genetic information in living organisms: how our DNA gets copied into RNA, which then gets converted into proteins, the building blocks of our cells, our bodies.
Originally, the RNA referred to in this equation—messenger RNA, or mRNA, the type that codes for proteins—was the only kind known to science. However, over the years, it has become clear that there are many, many other kinds.
“The world of RNA has proven to be a big and fascinating place,” says Marv Wickens, a CALS professor of biochemistry and leading pioneer in RNA research. “I’ve come to think of it as a Fellini movie, full of strange and unexpected characters.”
These Felliniesque characters are all the non-coding RNAs that exist in nature—the kinds that don’t code for proteins. They go by names like small interfering RNA, piwi-interacting RNA, microRNA, long non-coding RNA, small nuclear RNA—the list goes on and on. Together they far outnumber messenger RNAs in the cell; while only 3 percent of the human genome gets made into proteins (via messenger RNA), a full 80 percent gets copied into RNA.
What are all of these other RNAs doing? Lots of important and surprising things, scientists are discovering.
Over the past few decades, RNA, a close chemical cousin of DNA, has proven itself to be a much more versatile molecule than originally thought—far more than just a passive messenger.
The first big surprise came in the 1980s when it was shown that RNA can have catalytic activity, meaning that it can perform chemical reactions inside the cell. Originally assumed to be inert, like DNA, scientists found RNA molecules that could edit their own sequence—expunging a segment of their own genetic code.
Later, RNAs were discovered at the heart of important cellular machines, or enzymes, performing critical catalytic reactions, including those at the heart of the cell’s information transfer system. Previously only proteins were thought capable of such enzymatic feats.
These findings, it’s interesting to note, support the idea that RNA may be the original material of life. With them, RNA has two things going for it: it’s made of heritable genetic material and it’s chemically active.
“You could imagine you have a little RNA molecule that develops the capacity to copy itself—and now you’re off,” says Wickens.
More recently, scientists were surprised to discover that microRNAs, which are short pieces of non-coding RNA, play a major role in regulating gene expression. They do so by binding directly to messenger RNAs and altering the amount of protein the messenger RNAs produce. Scientists now believe that microRNAs may be regulating as many as 60 percent of human genes this way.
“It was a revolution. These microRNAs had been completely invisible to us,” says Wickens. “We now know that there are hundreds of these RNAs that affect gene expression. They’re involved in cancer and in other diseases—they’re everywhere.”
Yet many RNA mysteries remain. And CALS researchers, as they have been for decades, are at the forefront of efforts to explore these unknowns, working from a variety of angles to shed light—sometimes quite literally, using lasers—on the next big questions in the field.
“For a while, RNA was kind of like the dark matter inside the cell. Everything was below the radar,” says CALS biochemistry professor Sam Butcher. “Now we’re at the point where we know it’s there, and we’re working to figure out what’s going on.”
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