KATRINA CABALTERA, UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
N. Kondrashov et al., “Ribosome-mediated specificity in Hox mRNA translation and vertebrate tissue patterning,” Cell, 145:383-97, 2011. Free F1000 Evaluation
The ribosome was thought to treat all messenger RNAs the same, connecting coded peptides into a protein chain like a mindless machine. However, Maria Barna, a developmental biologist at the University of California, San Francisco, and colleagues found that a deletion in one ribosomal protein was responsible for skeletal abnormalities, such as kinked tails and extra ribs, in a line of mice called Ts for “tail short.” The ribosomal mutation caused decreased translation in eight of the 39 murine Hox genes, and suggests that ribosomes can regulate gene expression.
Barna screened the Ts mice for genetic abnormalities. Rather than finding one in Hox genes, as she had expected, she found deletion mutations in the gene that coded for RPL38, a ribosomal protein. Expecting mRNA translation to be affected across the board, they measured the levels of mRNAs bound to ribosomes and found that only the translation of certain Hox mRNAs was diminished.
The change in dogma
“Basically what it suggests is that the ribosome itself is helping to select the messages that it translates,” said Jonathan Warner, professor of cell biology at Albert Einstein College of Medicine. “This is the first time they’ve shown this.”
In humans, abnormal ribosomal-protein gene expression has been linked to diseases such as Diamond-Blackfan anemia. Barna says that she and her team are systematically deleting all the ribosomal proteins in mice to look for phenotypes that may one day inform understanding of this and similar developmental defects in humans.