Unlocking the Secrets of Gene Regulation in Fruit Flies
Professor Bomyi Lim's team found that enhancer strength and long introns, but not promoters or exon length, change how fast RNA polymerase II moves along genes in fruit fly embryos.
Transcription, a crucial step in how our genes express themselves, involves three stages: initiation, elongation, and termination, each controlled by a specific set of proteins. While the importance of the starting stage (initiation) is well-understood, the elongation phase is now seen as equally vital in controlling gene expression. The recent study led by, Professor Bomyi Lim alongside colleagues Dr. Samuel Keller and Hao Deng from University of Pennsylvania, explored how different regulatory DNAs and structural features of genes shape the rate at which RNA polymerase II (RNA Pol II) travels on the gene in living fruit fly embryos. Employing innovative live imaging techniques, the researchers tracked and visualized newly made RNAs in living cells, and precisely measured the pace at which RNA Pol II moves along the gene body.
They showed that the choice of promoters and the length of the coding part of genes (exons) do not change this rate. Conversely, the strengths of enhancers (regulatory DNAs) markedly impact the speed of RNA Pol II’s elongation, such that an enhancer that leads to more mRNA production exhibits a slower RNA Pol II elongation rate. Their investigation also revealed that adding long non-coding sequences (introns) to a gene’s structure increases the pace at which RNA Pol II elongates the gene, unlike genes with only short introns. Another key discovery of their research is the changing nature of the RNA Pol II elongation rate. The team noticed an acceleration of this rate after the initial start of gene copying during a specific developmental stage in the fruit fly embryo, using a more sophisticated analysis method.
Professor Bomyi Lim and colleagues have significantly advanced our understanding of the role played by RNA Pol II in regulating genes. Their research, published in Cell Reports, is a notable leap in understanding how DNAs are transcribed into messenger RNA (mRNA). This study not only deepens our understanding of RNA Pol II behavior during transcription but also paves the way for future research in gene regulation, offering valuable insights for a wide range of biological studies.
About the researchers
Dr. Bomyi Lim
Dr. Bomyi Lim is an assistant professor in the Department of Chemical and Biomolecular Engineering, and a secondary member of the Department of Cell and Developmental Biology at the Perelman School of Medicine. She obtained B.S. in Chemical and Biomolecular Engineering from University of Pennsylvania in 2010, and a Ph.D.… in Chemical and Biological Engineering from Princeton University in 2015. She worked as an NIH F32 postdoctoral fellow at the Lewis-Sigler Institute of Genomics at Princeton University, before coming to Penn as an assistant professor in 2018. The Lim lab focuses on characterizing the normal range of gene expression kinetics that ensures normal development, using a combination of genome editing, quantitative live imaging, and mathematical modeling. Bomyi received R35 Maximizing Investigators’ Research Award (MIRA) for early-stage investigators in 2020 and the NSF CAREER award in 2021.
Samuel Keller PhD
Samuel Keller PhD completed his B.S. in Chemical Engineering from Rensselaer Polytechnic Institute followed immediately by a PhD in Chemical and Biomolecular Engineering at the University of Pennsylvania.… His graduate research focused on quantitative gene expression in fruit flies using fluorescence confocal microscopy to assess the impact of transcription factors on gene expression and RNA polymerase II elongation rate. Currently, Samuel is completing a post-doctoral fellowship at Merck & Co. where he is studying HIV. His work focuses on understanding the latent reservoir of HIV and factors contributing to persistence of the virus in tissue.
Hao Deng
Hao Deng is a doctoral candidate in chemical and biomolecular engineering at the University of Pennsylvania. He received his BS in chemical and biomolecular engineering from the University of Illinois at Urbana-Champaign. His research focuses on the dynamics of the interplay between transcriptional components in Drosophila models with confocal microscopy.… He investigated the interallelic interactions between enhancers in hemizygotes and the enhancer-promoter interactions in trans with transvection assay. He is passionate about learning cutting-edge techniques and utilizing them to shine a different light on complicated problems.
Journal reference
Keller S.H., Deng H., Lim B. “Regulation of the dynamic RNA Pol II elongation rate in Drosophila embryos.” Cell Reports 42, 2023. DOI: https://doi.org/10.1016/j.celrep.2023.113225
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