Abstract
For the past fifty-five years, much of my research has focused on the function and biogenesis of red blood cells, including the cloning and study of many membrane proteins such as glucose and anion transporters and the erythropoietin receptor. We have also elucidated the mechanisms of membrane insertion, folding, and maturation of many plasma membrane and secreted proteins. Despite all of this work and more, I remain extremely proud of our very early work on the regulation of mRNA translation: work on bacteriophage f2 RNA in the 1960s and on translation of α- and β-globin mRNAs in the early 1970s. Using techniques hopelessly antiquated by today's standards, we correctly elucidated many important aspects of translational control, and I thought readers would be interested in learning how we did these experiments.
Highlights
My Own Early Years and Development as an Independent ScientistI was born in Cleveland, Ohio, on November 16, 1941
In the 1970s, in my laboratory at Massachusetts Institute of Technology (MIT), we studied the biogenesis of several red cell membrane proteins (4 –7)
In 1989, we reported the cloning of the erythropoietin receptor and the identification of the cytokine receptor superfamily [16, 17], and this has led to a long and ongoing set of projects on the activation of and signal transduction by the erythropoietin receptor in erythroid progenitor cells and the regulation of transcription, apoptosis, cell division, and enucleation during erythropoiesis (Refs. 18 –21; see older work reviewed in Refs. 22–25)
Summary
I was born in Cleveland, Ohio, on November 16, 1941. My father was a manager at a small company manufacturing electrical fittings for houses and autos, and my mother was a teacher before her marriage. Later in my own laboratory at MIT, I focused on understanding the mechanisms underlying the differential rates of initiation of translation of bacterial and bacteriophage mRNAs. First, together with Hugh Robertson, a Ph.D. student with Zinder at Rockefeller, we showed definitively that the third f2 protein produced in an E. coli cell-free system was the maturation protein [33] and that nascent f2 RNAs could direct synthesis of all three phage proteins [34]. Together with Hugh Robertson, a Ph.D. student with Zinder at Rockefeller, we showed definitively that the third f2 protein produced in an E. coli cell-free system was the maturation protein [33] and that nascent f2 RNAs could direct synthesis of all three phage proteins [34] During this period, initiation factors for protein synthesis were being identified and purified, and a major question was whether initiation factors or ribosomes regulated the rates or specificities of polypeptide chain initiation. I carried out several other experiments to show that RNA secondary structure restricted initiation of both the f2 maturation protein and RNA polymerase genes; chemical or thermal melting of the RNA increased initiation of translation of these genes by manyfold (36 –38)
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