Part II: Regulatory Effects of Mammalian micro-RNAs
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MicroRNAs are ~22 nucleotide RNAs processed from RNA hairpin structures. MicroRNAs are much too short to code for protein and instead play important roles in regulating gene expression. In humans, they regulate most protein-coding genes, including genes important in cancer and other diseases. In Part 1 of his talk, Bartel explains how microRNAs are made, how they have evolved, how they recognize and bind to target mRNA sequences, how this binding leads to the repression of the target mRNAs, and how this repression can be important for normal development and disease.
In Part 2, Bartel recounts experiments measuring the effect of microRNAs on mRNA levels, protein levels and protein synthesis in mammalian cells. The results showed that almost all of the changes in protein levels and synthesis are due to changes in the amount of mRNA. Interestingly, experiments in zebrafish embryos describe a somewhat different situation. In the early embryo, initial decreases in protein synthesis are due to shortening of the mRNA polyA tail, which is followed later by a decrease in the amount of RNA.
In the last part of his seminar, Bartel asks how a cell knows which hairpin RNA molecules are pre-microRNAs, and should be processed into microRNAs, and which should be ignored. He leads us through the experiments that identified some of the key conserved features of human pre-microRNAs.
David Bartel studies the many roles of RNA. His lab initially studied the ability of RNA to catalyze reactions and more recently has focused on microRNAs and other regulatory RNAs. Since 2000, his lab has made fundamental discoveries regarding the genomics, biogenesis and regulatory targets of these RNAs, as well as the molecular and biological consequences of their actions in animals, plants and fungi.
Bartel received his BA in Biology from Goshen College. Soon after completion of his PhD at Harvard University in 1993, he joined the Whitehead Institute as a Fellow. Currently, Bartel is Professor of Biology at the Massachusetts Institute of Technology, a Member of the Whitehead Institute and an Investigator of the Howard Hughes Medical Institute.
Bartel’s many contributions to our understanding of the roles of RNA have been recognized with numerous awards, including the NAS Molecular Biology Award and election to the National Academy of Sciences.
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Bartel, D.P. 2009. MicroRNAs: Target recognition and regulatory functions. Cell 136:215–233 (review).
Baek, D., J. Villen, C. Shin, F.D. Camargo, S.P. Gygi, and D.P. Bartel. 2008. The impact of microRNAs on protein output. Nature 455:64–71.
Guo, H., N.T. Ingolia, J.S. Weissman, and D.P. Bartel. 2010. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 466:835–840.
Subtelny, A.O., S.W. Eichhorn, G.R. Chen, H. Sive, and D.P. Bartel. 2014. Poly(A)-tail profiling reveals an embryonic switch in translational control. Nature, published online.
Chiang, H.R., L.W. Schoenfeld, J.G. Ruby, V.C. Auyeung, N. Spies, D. Baek, W.K. Johnston, C. Russ, S. Luo, J.E. Babiarz, R. Blelloch, G.P. Schroth, C. Nusbaum, and D.P. Bartel. 2010. Mammalian microRNAs: Experimental evaluation of novel and previously annotated genes. Genes Dev. 15:992–1009.
Auyeung, V.C., I. Ulitsky, S.E. McGeary, and D.P. Bartel. 2013. Beyond secondary structure: primary-sequence determinants license pri-miRNA hairpins for processing. Cell 152:844–858.