Researchers Visualize Proteins Being Born

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Mouse neuron showing mRNA molecules (red dots) and mature proteins (dim green dots). Sites showing mRNAs being actively translated into proteins are yellow (red mRNA plus multiple newly synthesized green proteins).

Einstein scientists have developed a technology allowing them to “see” single molecules of messenger RNA as they are translated into proteins in living mammalian cells. The findings, which may shed light on neurological diseases and cancer, were published online in May in Science.

“Genome-wide studies show that translation controls protein abundance in cells—important to every single function that cells carry out,” says Robert H. Singer, Ph.D., the paper’s senior author, co-chair of anatomy and structural biology and co-director of the Gruss Lipper Biophotonics Center at Einstein. “Using this technology, we can finally learn how translation is regulated and gain insights into diseases that occur when translation is faulty.” Dr. Singer also is co-director of the EGL Charitable Foundation Integrated Imaging Program and holds the Harold and Muriel Block Chair in Anatomy and Structural Biology.

Protein production starts in the cell nucleus, when protein-making information encoded in a gene’s DNA is transcribed into molecules of messenger RNA (mRNA). In the next step, called translation, the mRNA molecules hook up with molecular structures called ribosomes. Using mRNA as their blueprint, the ribosomes generate proteins by linking amino acids.

The scientists made a surprising finding in mouse neurons, where mRNA translation into protein was found to occur in “bursts”—a phenomenon never before possible to observe. “Bursts of translation activity may be the best way for neurons to control the amount and location of protein production—and neurological disease may result from neurons’ inability to control that bursting,” says Dr. Singer. “So our findings may have implications for intellectual disorders such as fragile X syndrome, which seem to involve too much protein production, and for neurodegenerative disorders such as Alzheimer’s, in which clumps of beta-amyloid protein may block neuron-to-neuron signaling at synapses.”

Another surprising observation occurred in cancer cells, where the researchers noted a striking inability to regulate the translation of mRNA. Instead, mRNA translation was continuous. Since proteins play crucial roles in controlling cell division, the uncontrolled translation of certain proteins may lead to certain types of cancer.

“With our technology, researchers can now study disease-causing protein aberrations at a basic level that was never possible before,” says Dr. Singer, also a professor in the department of cell biology and in the Dominick P. Purpura Department of Neuroscience.