Every living cell is a metropolis in which the vast bulk of work is performed by phenomenally productive laborers called proteins. Proteins work so hard - and the work that must be done in a cell changes so rapidly - that turnover in the labor force is immense. To maintain the brisk pace of life inside a cell, new proteins must constantly be assembled.
The machines responsible for that assembly are called ribosomes - as many as 10 million of them within a single mammalian cell, each capable of stapling together up to 200 amino acids (the building blocks of proteins) per second. The resulting amino-acid strings immediately fold themselves into characteristic structures reflecting their precise composition.
There are about 20 different varieties of amino acids, so the number of possible combinations a ribosome can make, in theory, is mind-boggling. But a ribosome doesn't just piece together whatever protein suits its passing fancy. It carefully heeds instructions stored on lengthy strands of DNA inside the cell's nucleus, in a massive library known as the genome: a gigantic set of genes (the recipes for proteins), written in a ribosome-readable chemical code. But genes never leave the nucleus, and ribosomes never enter it.
Bridging that physical gap is a substance called messenger RNA, chemically similar to DNA but physically far more flexible and athletic. Like couriers carrying copies of a royal edict, messenger RNA molecules constantly exit the nucleus, where they were produced as portable copies of one gene or another. They head for the watery suburbs of the cell where protein construction takes place. And there, they find a ribosome, climb in, are fed through the ribosome's molecular machinery, and get spit out like spent ticker tape once the ribosome has finished reading the recipe and assembling the specified protein product.
Under ordinary circumstances, ribosomes faithfully follow genetic instructions. But with all that whirling and whirring, sometimes things go wrong: The mRNA molecule or the ribosome is defective or, for some other reason, the protein-in-the-making is faulty.
Misspelled or misfolded proteins can wreak havoc. Happily, cells have "quality control" teams that can pick apart poorly produced proteins, tear up malfunctioning messenger RNA and retire rotten ribosomes.
In exploring that process, Stanford biochemist Onn Brandman, PhD, and colleagues at the University of California and University of Utah may have turned molecular-biological dogma on its head. In a new study in Science, Brandman and his associates report that they've identified a member of the quality-control squad, a protein called rqc2, that gloms onto stalled ribosomes - and then does something no protein has ever previously been shown to do: call out for the delivery of two particular amino acids, which get attached in random sequences to the aberrant protein under construction.
"Our results defy textbook science, showing for the first time that the building blocks of a protein, amino acids, can be assembled without the standard blueprints," Brandman told me. "In the case we observed, neither DNA nor messenger RNA but a protein directs that a pair of amino acids be randomly added, in small stretches, to the ends of proteins that have stalled mid-synthesis. The function of these 'tails' isn't known. But in yeast, elevated levels are correlated with proteotoxic stress, a condition that in humans may be involved in disorders such as Alzheimer's, Parkinson's and Huntington's disease."
Previously: Key to naked mole rat longevity may be related to their body's ability to make proteins accurately and Night of the living dead gene: Pseudogene wakes up, puts chill on inflammation
Photo by Iain Farrell
