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CCB Seminar: Regulation of stem cell homeostasis – The role of a ribosomal RNA intron

October 5, 2020 @ 1:00 pm - 2:00 pm

Dr. Eliezer Calo, Department of Biology, MIT
The balancing of cell growth with cell division determines the overall rates of cell proliferation and the emergence of form and function during metazoan development. The commitment to growth and, consequently, proliferate or differentiate is underpinned by a cell’s protein synthesis capacity. How protein synthesis allows cells to coordinate their growth with their division remains largely mysterious. To start gaining insights into these mechanisms my lab employed a proteomic strategy to purified the small subunit (SSU) processome, the molecular chaperone in the cell that assembles the small subunit of the ribosome. The assembly of the SSU processome initiates the biogenesis of ribosomes and is the single most important step during ribosome production. We successfully identified all the conserved components of the eukaryotic SSU processome and many novel factors. Among them was DNA-dependent protein kinase (DNA-PK). We generated mice in which DNA-PK is catalytically inactive and found that these animals were born with macrocytic anemia and die of bone marrow failure. The blocking of DNA-PK kinase activity prevented the assembly of the SSU processome and impaired protein synthesis rates in the hematopoietic stem cells. At the molecular level, we find that DNA-PK kinase activity was stimulated when DNA-PK bound to non-coding RNAs that are essential for the assembly of the SSU processome. Together, our results identified DNA-PK as a cellular kinase that enables the regulated production of proteins in Hematopoietic stem cells.
Eliezer Calo was born and raised in Puerto Rico. He was the first in his family to attend college. He obtained a bachelor’s degree in Chemistry from the University of Puerto Rico, Río Piedras Campus and a Ph.D. in Biology from the Massachusetts Institute of Technology. For postdoctoral training, he attended Stanford University and was awarded with the prestigious Helen Hay Whitney postdoctoral fellowship. Currently, he is an assistant professor in the Department of Biology at the Massachusetts Institute of Technology. He is the recipient of the Basil O’Connor Starter Scholar and Charles H. Hood Foundation Child Health Research Awards and was named a 2019 Pew Scholar.


October 5, 2020
1:00 pm - 2:00 pm


Zoom Seminar