Department of Molecular Genetics and Microbiology
Amino Acid Sequence; Base Sequence; Binding Sites; DNA, Fungal; Exoribonucleases; Genes, Fungal; Models, Molecular; Molecular Sequence Data; Mutation; Peptide Mapping; Poly(A)-Binding Proteins; Protein Structure, Tertiary; Protein Subunits; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Two-Hybrid System Techniques
Life Sciences | Medicine and Health Sciences
PAN, a yeast poly(A) nuclease, plays an important nuclear role in the posttranscriptional maturation of mRNA poly(A) tails. The activity of this enzyme is dependent on its Pan2p and Pan3p subunits, as well as the presence of poly(A)-binding protein (Pab1p). We have identified and characterized the associated network of factors controlling the maturation of mRNA poly(A) tails in yeast and defined its relevant protein-protein interactions. Pan3p, a positive regulator of PAN activity, interacts with Pab1p, thus providing substrate specificity for this nuclease. Pab1p also regulates poly(A) tail trimming by interacting with Pbp1p, a factor that appears to negatively regulate PAN. Pan3p and Pbp1p both interact with themselves and with the C terminus of Pab1p. However, the domains required for Pan3p and Pbp1p binding on Pab1p are distinct. Single amino acid changes that disrupt Pan3p interaction with Pab1p have been identified and define a binding pocket in helices 2 and 3 of Pab1p's carboxy terminus. The importance of these amino acids for Pab1p-Pan3p interaction, and poly(A) tail regulation, is underscored by experiments demonstrating that strains harboring substitutions in these residues accumulate mRNAs with long poly(A) tails in vivo.
DOI of Published Version
Mol Cell Biol. 2004 Jun;24(12):5521-33. Link to article on publisher's site
Molecular and cellular biology
Mangus DA, Evans MC, Agrin NS, Smith MM, Gongidi P, Jacobson A. (2004). Positive and negative regulation of poly(A) nuclease. Open Access Publications by UMMS Authors. https://doi.org/10.1128/MCB.24.12.5521-5533.2004. Retrieved from https://escholarship.umassmed.edu/oapubs/1420