The Rqc2 protein (yellow) binds tRNAs (dark blue, teal) which add amino acids (bright spot in middle) to a partially made protein (green); the complex binds the ribosome (white). Image credit: Janet Iwasa / University of Utah.
“This surprising discovery reflects how incomplete our understanding of biology is. Nature is capable of more than we realize,” said Dr Peter Shen of the University of Utah, the lead author of the paper published in the journal Science.
To put the new finding into perspective, it might help to think of the cell as a well-run factory.
“Ribosomes are machines on a protein assembly line, linking together amino acids in an order specified by the genetic code. When something goes wrong, the ribosome can stall, and a quality control crew is summoned to the site. To clean up the mess, the ribosome is disassembled, the blueprint is discarded, and the partly made protein is recycled,” the scientists said.
Yet the new study reveals a surprising role for one member of the quality control team, a protein conserved from yeast to man named Rqc2. Before the incomplete protein is recycled, Rqc2 prompts the ribosomes to add just two amino acids – alanine and threonine – over and over, and in any order.
“Think of an auto assembly line that keeps going despite having lost its instructions. It picks up what it can and slaps it on: horn-wheel-wheel-horn-wheel-wheel-wheel-wheel-horn.”
Prof Frost added: “in this case, we have a protein playing a role normally filled by mRNA.”
Like a half-made car with extra horns and wheels tacked to one end, a truncated protein with an apparently random sequence of alanines and threonines looks strange, and probably doesn’t work normally.
But the nonsensical sequence likely serves specific purposes. The code could signal that the partial protein must be destroyed, or it could be part of a test to see whether the ribosome is working properly.
Evidence suggests that either or both of these processes could be faulty in neurodegenerative diseases such as Alzheimer’s, Amyotrophic lateral sclerosis, or Huntington’s.
“There are many interesting implications of this work and none of them would have been possible if we didn’t follow our curiosity. The primary driver of discovery has been exploring what you see, and that’s what we did. There will never be a substitute for that,” said study co-author Dr Onn Brandman of Stanford University.
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Peter S. Shen et al. 2015. Rqc2p and 60S ribosomal subunits mediate mRNA-independent elongation of nascent chains. Science, vol. 347, no. 6217, pp. 75-78; doi: 10.1126/science.1259724