Understanding the mechanisms by which upstream open reading frames (uORFs) in mRNA transcripts control gene expression is currently the major focus of my laboratory. A substantial component of this work is focused on the uORF-encoded fungal arginine attenuator peptide (AAP). The major goal of this work is to understand the mechanism by which a nascent peptide encoded by this uORF controls the movement of ribosomes on mRNA and regulates gene expression. Control mechanisms mediated by uORFs and nascent peptides exist in mammals, fungi, plants, viruses, and bacteria, but relatively little is known of the molecular details of such control. The AAP is encoded by a uORF in the 5?-leader regions of mRNAs specifying the first enzyme in fungal arginine (Arg) biosynthesis. Synthesis of the AAP rapidly reduces gene expression in response to Arg. AAP-mediated regulation is observed in vivo in both Neurospora crassa and Saccharomyces cerevisiae and in vitro, using fungal, plant and animal extracts. The nascent AAP causes the ribosome to stall when the concentration of Arg is high.
- Stanford University - (Stanford, California, United States), Postdoctoral Training 1990
- Ph.D. in Biology, Massachusetts Institute of Technology - (Cambridge, Massachusetts, United States) 1986
- A.B. in Biochemistry, Cornell University - (Ithaca, New York, United States) 1979
- van der Stel, A., Gordon, E. R., Sengupta, A., Martínez, A. K., Klepacki, D., Perry, T. N., ... Innis, C. A. (2021). Structural basis for the tryptophan sensitivity of TnaC-mediated ribosome stalling. Nature Communications. 12(1), 5340.
- Karki, S., Castillo, K., Ding, Z., Kerr, O., Lamb, T. M., Wu, C., Sachs, M. S., & Bell-Pedersen, D. (2020). Circadian clock control of eIF2α phosphorylation is necessary for rhythmic translation initiation. Proc Natl Acad Sci U S A. 117(20), 10935-10945.
- Yang, Q., Yu, C., Zhao, F., Dang, Y., Wu, C., Xie, P., Sachs, M. S., & Liu, Y. i. (2019). eRF1 mediates codon usage effects on mRNA translation efficiency through premature termination at rare codons. Nucleic Acids Research. 47(17), 9243-9258.
- Stavrianakou, M., Perez, R., Wu, C., Sachs, M. S., Aramayo, R., & Harlow, M. (2017). Draft de novo transcriptome assembly and proteome characterization of the electric lobe of Tetronarce californica: a molecular tool for the study of cholinergic neurotransmission in the electric organ. BMC GENOMICS. 18(1), 611.
- Li, H., Wu, C., Aramayo, R., Sachs, M. S., & Harlow, M. L. (2017). Synaptic vesicles isolated from the electric organ of Torpedo californica and from the central nervous system of Mus musculus contain small ribonucleic acids (sRNAs). Data in Brief. 12, 52-53.
- Hood, H. M., Neafsey, D. E., Galagan, J., & Sachs, M. S. (2009). Evolutionary Roles of Upstream Open Reading Frames in Mediating Gene Regulation in Fungi. Annual Reviews.
- Wu, C., Amrani, N., Jacobson, A., & Sachs, M. S. (2007). Chapter Ten The Use of Fungal In Vitro Systems for Studying Translational Regulation. Elsevier.
- Dunlap, J. C., Borkovich, K. A., Henn, M. R., Turner, G. E., Sachs, M. S., Glass, N. L., ... Xu, J. (2007). Enabling a Community to Dissect an Organism: Overview of the Neurospora Functional Genomics Project. Elsevier.
- Dever, T. E., Ivanov, I. P., & Sachs, M. S. (2020). Conserved Upstream Open Reading Frame Nascent Peptides that Control Translation. Annual Review of Genetics. ANNUAL REVIEW OF GENETICS, VOL 54, 2020. (pp. 1-28). Annual Reviews.
- Perkins, D. D., Radford, A., & Sachs, M. S. (2001). Information on Individual Loci. The Neurospora Compendium. (pp. 7-197). Elsevier.
- Perkins, D. D., Radford, A., & Sachs, M. S. (2001). Introduction. The Neurospora Compendium. (pp. 1-6). Elsevier.
- Perkins, D., Radford, A., & Sachs, M. (2001). Preface. The Neurospora Compendium. (pp. vii-vii). Elsevier.
- Schroeder, A. L., Inoue, H., & Sachs, M. S. (1998). DNA Repair in Neurospora. DNA Damage and Repair. (pp. 503-538). Humana Press.
- Doamekpor, S. K., Lee, J., Hepowit, N. L., Wu, C., Charenton, C., Leonard, M., ... Joazeiro, C. (2016). Structure and function of the yeast listerin (Ltn1) conserved N-terminal domain in binding to stalled 60S ribosomal subunits. Proc Natl Acad Sci U S A. 113(29), e4151-e4160.