Robert Singer, PhD

Professor and Chair
Department of Neuroscience, Anatomy and Structural Biology, and Cell Biology
Albert Einstein College of Medicine
April 16, 2019

Following Single mRNAs from Life to Death in Living Cells

Synthesis of messenger RNA (mRNA) is an essential step in the translation of DNA codes to protein. In the neuron, mRNA can live at the area of a synapse, ready for protein synthesis. In his talk, Dr. Singer discussed the importance of imaging mRNAs throughout their life-cycle, from birth to degradation. His research has involved tagging mRNA with markers that glow under a microscope, allowing for imaging of the molecules in living tissues. As genetic material is relayed via mRNA, understanding their mechanisms is essential.

The Singer Lab has developed a myriad of molecular tools which tag cell molecules with fluorescent markers. Once inserted into animals mRNA can be followed in living tissue. By imaging these mRNAs as they are born and diffuse through the nucleus, exit through the nuclear pores and move into the cytoplasm to be actively localized at particular regions in the cytoplasm, and by observing the kinetics of these events, insights can be revealed concerning the mechanisms involved. For instance, mRNAs are translationally repressed, especially in neurons, until they arrive at a specific location such as an incipient synapse where the synthesis of proteins stabilize the synaptic contact, hence providing a cellular mechanism for learning and memory. A tool to determine how, when and where individual mRNAs are translated has provided valuable information on the regulation of protein synthesis.

What remains to be determined is how and when mRNAs are chosen for degradation. Evidence on cell cycle regulated mRNAs indicates that these mRNAs are marked at the time of transcription to be degraded at a particular point in the cell cycle, hence completing the circle of life for these molecules and allowing the cell to progress into mitosis. Development of new tools for monitoring the stages of mRNA expression in living cells and animals will illuminate regulatory mechanisms not yet imagined.