Polyadenylation-dependent gene regulation
Oculopharyngeal muscular dystrophy (OPMD) is an inherited disease caused by mutations in the gene encoding PABPN1 (Poly(A)-Binding Protein Nuclear 1). As the function of PABPN1 remains poorly understood, the molecular basis of OPMD has remained elusive. Our group has made breakthroughs in determining the function of PABPN1.
We generated the first yeast model by identifying Pab2, the fission yeast homolog of PABPN1. We also uncovered Pab2’s unexpected role in the regulation of noncoding (nc) RNAs. Importantly, we showed that human PABPN1 promotes the nuclear turnover of several long ncRNAs and the maturation of the telomerase RNA. Our work has unveiled a conserved mode of polyadenylation-dependent gene regulation whereby PABPN1 promotes RNA decay in the nucleus to prevent untimely expression.
Nguyen, D., V. Grenier St-Sauveur, D. Bergeron, F. Dupuis-Sandoval, M. S. Scott and F. Bachand (2015). “A Polyadenylation-Dependent 3′ End Maturation Pathway Is Required for the Synthesis of the Human Telomerase RNA.” Cell Rep 13: 2244-2257.
Beaulieu, Y. B., C. L. Kleinman, A. M. Landry-Voyer, J. Majewski and F. Bachand (2012). “Polyadenylation-dependent control of long noncoding RNA expression by the poly(A)-binding protein nuclear 1.” PLoS Genet 8: e1003078. http://www.ncbi.nlm.nih.gov/pubmed/23166521
Lemay, J. F., A. D’Amours, C. Lemieux, D. H. Lackner, V. G. St-Sauveur, J. Bahler and F. Bachand (2010). “The nuclear poly(A)-binding protein interacts with the exosome to promote synthesis of noncoding small nucleolar RNAs.” Mol Cell 37: 34-45. https://www.ncbi.nlm.nih.gov/pubmed/20129053
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Recent studies indicate that transcription is pervasive in eukaryotes, producing a complex network of noncoding RNAs (ncRNAs) that exist stably in cells or are rapidly degraded.