A primer on RNA, perhaps the most consequential molecule of all
“The Catalyst” looks at RNA’s role in life’s origins as well as its medical uses
What you see depends on how you look. For years students of cell biology were taught that a molecule called RNA was but a humble minion assisting its glamorous cousins, DNA and proteins. DNA acted as the library of all knowledge about how to build an organism and proteins the means by which that organism was built. RNA, by contrast, was seen as a messenger boy, carrying copies of DNA’s blueprints to the cellular workshops where proteins were forged; a porter, toting the amino-acid links of protein chains to those workshops for assembly; and a part of the fabric of the workshops themselves.
But, like someone staring at a Necker cube, biologists now realise that this picture can be viewed another way—one that puts RNA centre stage. Their shift of perception has followed the gradual realisation that RNA has a far wider range of jobs in cells than previously understood. Indeed, it seems likely that RNA actually predates the other two members of the trio as the original molecule of life itself.
All this is the subject of Thomas Cech’s new book, “The Catalyst”. The author is well-placed to describe how this perceptual shift happened, given that he was one of the early dissenters who brought it about. In the 1980s he championed the idea that RNA molecules can also act as enzymes—that is, as catalysts for biochemical reactions—a claim which flew in the face of the conventional wisdom that only proteins could perform such manoeuvres. In 1989 he shared the Nobel Chemistry Prize for the discovery of what his team dubbed “ribozymes”.
The particular ribozymal activity Dr Cech’s team found was an “autocatalytic” rearrangement of an RNA molecule (the actual discovery was made by Paula Grabowski, a graduate student). The molecule was destined to become part of a ribosome—as the protein workshops are properly called—and part of the molecule cut out another, redundant, part. That may sound trivial. But it blew the enzymes-are-always-proteins dogma out of the water.
Similar discoveries by other labs quickly followed, as did other types of ribozyme which did different jobs. Indeed it turned out that the RNA in ribosomes is not just structural, but also catalytic. It is this, not a ribosome’s protein component, which does the work of adding amino acids to a growing protein chain.
That discovery, in particular, excited scientists seeking life’s origin. The complex arrangement whereby proteinaceous enzymes (which orchestrate a cell’s chemistry) are encoded by DNA (which does the information storage) could not have appeared from anything. But if RNA can do both jobs (which it can), then the earliest critters may have relied on it alone. Only once RNA-based organisms were up and running, the thinking now goes, was information storage then handed over by evolution to DNA (which is more stable than RNA) and catalysis to proteins (the chemical complexity of which permits a bigger range of enzymes), with RNA assuming its current roles linking these other two types of molecules.
The number of known links is multiplying. Since Dr Cech’s original discovery, many other types of RNA have manifested themselves, involved either in gene regulation or in protecting cells against viral infection. This growing list affords medical and biotechnological opportunities. About half of antibiotics, for example, work by gumming up the RNA in bacterial ribosomes while leaving that in humans unharmed. This is a promising starting point in the search for new drugs.
RNA can also work to silence disease-causing genetic mutations. Scientists can craft versions of RNA that pair up with, and disable, RNA messengers from the mutated DNA section. RNA messengers have also been used to create covid-busting vaccines and may soon be deployed against other diseases, including certain types of cancer. And RNA is a crucial element of the modern suite of gene-editing techniques that began with CRISPR-Cas9. Not a bad record, then, for what was once molecular biology’s also-ran.
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