Open any introductory biology textbook and one of the first things you’ll learn is that our DNA spells out the instructions for making proteins, tiny machines that do much of the work in our body’s cells.
Results from a study published on Jan. 2 in Science defy textbook science, showing for the first time that the building blocks of a protein, called amino acids, can be assembled without blueprints – DNA and an intermediate template called messenger RNA (mRNA). A team of researchers has observed a case in which another protein specifies which amino acids are added.
Janet Iwasa, Ph.D., University of Utah
Caught in the act: Rqc2 protein adds amino acids to a new protein A new finding goes against dogma, showing for the first time that the building blocks of a protein, called amino acids, can be assembled by another protein, and without genetic instructions. 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).
“This surprising discovery reflects how incomplete our understanding of biology is,” says first author Peter Shen, Ph.D., a postdoctoral fellow in biochemistry at the University of Utah. “Nature is capable of more than we realize.”
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.
Yet this 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 (of 20 total) – 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.
“In this case, we have a protein, Rqc2, playing a role similar to that of mRNA,” says Adam Frost, M.D., Ph.D., assistant professor at University of California, San Francisco (UCSF) and adjunct professor of biochemistry at the University of Utah. He shares senior authorship with Jonathan Weissman, Ph.D., a Howard Hughes Medical Institute investigator at UCSF, and Onn Brandman, Ph.D., at Stanford University. “I love this story because it blurs the lines of what we thought proteins could do.”
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 (ALS), 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,” says Brandman. “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.”
The scientists first considered the unusual phenomenon when they saw evidence of it with their own eyes. They fine-tuned a technique called cryo-electron microscopy to flash freeze, and then visualize, the quality control machinery in action. “We caught Rqc2 in the act,” says Frost. “But the idea was so far-fetched. The onus was on us to prove it.”
It took extensive biochemical analysis to validate their hypothesis. New RNA sequencing techniques showed that the Rqc2/ribosome complex had the potential to add amino acids to stalled proteins because it also bound tRNAs, structures that bring amino acids to the protein assembly line. The specific tRNAs they saw only carry the amino acids alanine and threonine. The clincher came when they determined that the stalled proteins had extensive chains of alanines and threonines added to them.
“Our job now is to determine when and where this process happens, and what happens when it fails,” says Frost.
Shen, Frost, Brandman, and Weissman conducted the work in collaboration with colleagues at the University of Utah (Krishna Parsawar, James Cox), University of California at San Francisco (Xueming Li, Yifan Cheng, Matthew Larson), Stanford University (Joseph Park), and the University of Texas at Austin (Yidan Qin, Alan Lambowitz).
The research was supported by grants from the Searle Scholars program, the National Institutes of Health, the Howard Hughes Medical Institute, Stanford University, and the University of Utah.
Rqc2p and 60S ribosomal subunits mediate mRNA-independent elongation of nascent chains. Peter S. Shen, Joseph Park, Yidan Qin, Xueming Li, Krishna Parsawar, Matthew H. Larson, James Cox, Yifan Cheng, Alan M. Lambowitz, Jonathan S. Weissman, Onn Brandman, Adam Frost. Science, Jan. 2, 2015
Julie Kiefer | newswise
Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel
The Nagoya Protocol Creates Disadvantages for Many Countries when Applied to Microorganisms
05.12.2016 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
05.12.2016 | Power and Electrical Engineering
05.12.2016 | Materials Sciences
05.12.2016 | Power and Electrical Engineering