Abstract

This proposal utilizes the cellular slime mold, Dictyostelium discoideum, to consider two problems of post-transcriptional regulation of gene expression: 1) What is the function of poly(A)? and 2) What are the determinants of mRNA stability? We postulate that poly(A) tails do not regulate mRNA stability, but rather that they have a role in protein synthesis that is mediated by the cytoplasmic poly(A)-binding proteins. The first half of this proposal addresses this hypothesis by: a) determining the translational efficiency and poly(A) tail length of individual mRNAs in growing and developing cells, b) characterizing specific binding properties of the poly(A)-binding proteins and c) testing whether antibodies which recognize the poly(A)-binding proteins can inhibit protein synthesis in vitro. The experiments of the second half of this proposal will consider alternate explanations for the regulation of mRNA stability. Two sets of cDNAs which encode stable or unstable mRNAs, respectively, have been cloned and will be used to compare the properties of these two classes of mRNA. We will determine whether mRNA stability correlates with translational efficiency or with the presence of specific 5' or 3' untranslated sequences, transcribed repetitive sequences, or poly(A). In addition, we will determine whether the half-lives of specific mRNAs are differentially regulated during the Dictyostelium life cycle.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM027757-07
Application #
3275016
Study Section
Molecular Biology Study Section (MBY)
Project Start
1980-04-01
Project End
1988-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
7
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Massachusetts Medical School Worcester
Department
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655

  Publications

He, Feng; Celik, Alper; Wu, Chan et al. (2018) General decapping activators target different subsets of inefficiently translated mRNAs. Elife 7:
Celik, Alper; Baker, Richard; He, Feng et al. (2017) High-resolution profiling of NMD targets in yeast reveals translational fidelity as a basis for substrate selection. RNA 23:735-748
Celik, Alper; He, Feng; Jacobson, Allan (2017) NMD monitors translational fidelity 24/7. Curr Genet 63:1007-1010
Jacobson, Allan (2017) The moment when translational control had a theory of everything. Nat Rev Mol Cell Biol 18:344
Roy, Bijoyita; Friesen, Westley J; Tomizawa, Yuki et al. (2016) Ataluren stimulates ribosomal selection of near-cognate tRNAs to promote nonsense suppression. Proc Natl Acad Sci U S A 113:12508-12513
He, Feng; Jacobson, Allan (2015) Nonsense-Mediated mRNA Decay: Degradation of Defective Transcripts Is Only Part of the Story. Annu Rev Genet 49:339-66
Jacobson, Allan (2015) Methods to our madness. RNA 21:529-30
Celik, Alper; Kervestin, Stephanie; Jacobson, Allan (2015) NMD: At the crossroads between translation termination and ribosome recycling. Biochimie 114:2-9
Roy, Bijoyita; Leszyk, John D; Mangus, David A et al. (2015) Nonsense suppression by near-cognate tRNAs employs alternative base pairing at codon positions 1 and 3. Proc Natl Acad Sci U S A 112:3038-43
He, Feng; Jacobson, Allan (2015) Control of mRNA decapping by positive and negative regulatory elements in the Dcp2 C-terminal domain. RNA 21:1633-47

Showing the most recent 10 out of 63 publications