Allan Jacobson, Ph.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Molecular Genetics and Microbiology

Other Affiliation(s):
   Interdisciplinary Graduate Program

Cytoplasmic Aspects of the Post-transcriptional Regulation of Gene Expression

Research in my laboratory is focused on the regulation of mRNA stability in the yeast Saccharomyces cerevisiae . Our efforts are currently focused on the mechanisms that dictate rapid decay of two classes of unstable mRNAs: those that are inherently unstable and those that are normally stable, but are destabilized by the presence of a premature nonsense codon. We are analyzing the function of coding sequence elements required for both types of rapid decay as well as isolating and characterizing mutants incapable of degrading either or both classes of mRNA. The latter approach has led to the identification of several trans -acting factors essential for mRNA degradation. Specific interactions of these factors are being analyzed by genetic approaches.

Recent Publications

Amrani N, Ghosh S, Mangus DA, Jacobson A.  Translation factors promote the formation of two states of the closed-loop mRNP. Nature, 2008 [Epub ahead of print]   Pubmed Link

Johansson MJ, He F, Spatrick P, Li C, Jacobson A.  Association of yeast Upf1p with direct substrates of the NMD pathway. Proc. Natl. Acad. Sci. U S A. 207: 20872-20877, 2007 Epub 2007 Dec 17.   Pubmed Link

Welch EM, etal, PTC124 targets genetic disorders caused by nonsense mutations.  Nature. 447: 87-91, 2007  Epub 2007 Apr 22.   Pubmed Link

Dong S, Li C, Zenklusen D, Singer RH, Jacobson A, He F. YRA1 autoregulation requires nuclear export and cytoplasmic Edc3p-mediated degradation of its pre-mRNA. Molec. Cell. 25: 559-573, 2007 Pubmed Link

Gaba A, Jacobson A, Sachs MS. Ribosome occupancy of the yeast CPA1 upstream open reading frame termination codon modulates nonsense-mediated mRNA decay.  Molec. Cell. 11: 449-460, 2005  Pubmed Link

Amrani N, Ganesan R, Kervestin S, Mangus DA, Ghosh S, Jacobson A.,A faux 3'-UTR promotes aberrant termination and triggers nonsense-mediated mRNA decay. Nature. 432:112-118, 2004. Pubmed Link

Ross PL, Huang YN, Marchese JN, Williamson B, Parker K, Hattan S, Khainovski N, Pillai S, Dey S, Daniels S, Purkayastha S, Juhasz P, Martin S, Bartlet-Jones M, He F, Jacobson A, Pappin DJ.  Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Molec. Cell Proteomics. 3:1154-1169, 2004. Epub 2004 Sep 22.  Pubmed Link

Mangus DA, Evans MC, Agrin NS, Smith M, Gongidi P, Jacobson A  Positive and negative regulation of poly(A) nuclease. Molec. Cell Biol. 24: 5521-5533, 2004. Pubmed Link

Mangus DA, Smith MM, McSweeney JM, Jacobson A. Identification of factors regulating poly(A) tail synthesis and maturation. Molec. Cell Biol. 24: 4196-206, 2004. Pubmed Link

Parker KC, Patterson D, Williamson B, Marchese J, Graber A, He F, Jacobson A, Juhasz P, Martin S. Depth of proteome issues: a yeast isotope-coded affinity tag reagent study. Molec. Cell Proteomics. 3: 625-659, 2004. Epub 2004 Mar 28. Pubmed Link

He F, Li X, Spatrick P, Casillo R, Dong S, Jacobson A.  Genome-wide analysis of mRNAs regulated by the nonsense-mediated and 5' to 3' mRNA decay pathways in yeast.   Molec. Cell. 12:  1439-1452, 2003 Pubmed Link

Mangus DA, Evans MC, Jacobson A.  Poly(A)-binding proteins: multifunctional scaffolds for the post-transcriptional control of gene expression.  Genome Biol. 4: 223. Epub 2003 Jul 1. Review. Pubmed Link

Maderazo AB, Belk JP, He F, Jacobson A.  Nonsense-containing mRNAs that accumulate in the absence of a functional nonsense-mediated mRNA decay pathway are destabilized rapidly upon its restitution. Molec. Cell Biol. 23:   842-851, 2003. Pubmed Link

Sachs MS, Wang Z, Gaba A, Fang P, Belk J, Ganesan R, Amrani N, Jacobson A. Toeprint analysis of the positioning of translation apparatus components at initiation and termination codons of fungal mRNAs. Methods. 26: 105-114, 2002. Pubmed Link

Düvel K, Valerius O, Mangus DA, Jacobson A, Braus GH.  Replacement of the yeast TRP4 3' untranslated region by a hammerhead ribozyme results in a stable and efficiently exported mRNA that lacks a poly(A) tail.  RNA. 8: 336-44, 2002  Pubmed Link

He, F. and Jacobson, A. Upf1p, Nmd2p, and Upf3p regulate the decapping and exonucleolytic degradation of both nonsense-containing mRNAs and wild-type mRNAs Molec. Cell. Biol. 21: 1515-1530, 2001.   Pubmed Link

Maderazo, A.B., He, F., Mangus, D.A., and Jacobson, A. Upf1p control of nonsense mRNA translation is regulated by Nmd2p and Upf3p. Molec. Cell. Biol. 20: 4591-4603, 2000. Pubmed Link

Review Articles

Wu C, Amrani N, Jacobson A, Sachs MS.  The use of fungal in vitro systems for studying translational regulation. (Review)  Methods Enzy. Molec. 429: 2007;203-225,2007 Pubmed Link

Amrani N, Sachs MS, Jacobson A. Early nonsense: mRNA decay solves a translational problem. Nat Rev Molec. Cell Biol. 7: 415-425, 2006. Review. Pubmed Link

Jacobson, A. The end justifies the means.  Nature Struct. Molec. Biol. 12: 474-475, 2005. Pubmed Link

Jacobson, A. Regulation of mRNA decay: decapping goes solo. Molec. Cell 15: 1-2, 2004. Pubmed Link

Mangus, D.A., Evans, M.C., and Jacobson, A. Poly(A)-binding proteins: multifunctional scaffolds for the post-transcriptional control of gene expression. Genome Biol. 4: 223.1-223.14, 2003.  Pubmed Link

Jacobson, A. and Peltz, S.W. Destabilization of nonsense-containing transcripts in Saccharomyces cerevisiae. In: Translational Control, Second Edition (Eds: N. Sonenberg, J.W.B. Hershey and M.B. Mathews), Cold Spring Harbor Laboratory Press, N.Y., pp. 827-847, 2000.

Rotation Projects

Gene Chip Analysis of Post-transcriptional Regulatory Events. Using the yeast Saccharomyces cerevisiae as a model system, we have identified several genes that regulate key steps in the pathways of mRNA decay. We are now seeking to determine whether these regulatory genes affect the stability of all cellular mRNAs, or just selected subsets of mRNAs. If the latter is true, we anticipate that structural comparisons of mRNAs that are or are not substrates of a given regulator should provide considerable insight into the mechanism of action of that regulator. To facilitate such global analyses of the behavior of all cellular mRNAs, we will exploit a new technology, gene chip analysis, and a new core facility established in our lab. The DNA chips (or high density DNA microarrays) allow the simultaneous analysis of all yeast mRNAs in a single experiment. For a rotation project, these chips would be used to monitor the levels of all yeast mRNAs in selected mRNA decay mutants and these levels would be compared to those obtained in wild-type strains. The student undertaking this project would learn about yeast genetics, RNA manipulation, gene chip analysis, intensive data analysis, and, ultimately, would gain insight into the mechanisms of post-transcriptional regulation in yeast and mammalian cells.

Academic Background

Ph. D. (1971) Brandeis University

Office: S5-117
Phone: 508-856-2442
E-mail: Allan.Jacobson@umassmed.edu
Keywords: Genetic Systems, Gene Expression

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