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Regulation of Gene Expression by non-canonical poly(A) and poly(U) polymerases

Final Report Summary - PAPS&PUPS (Regulation of Gene Expression by non-canonical poly(A) and poly(U) polymerases)

In eukaryotes, gene expression is regulated at multiple levels. Initially, researchers focused on the regulation of transcription, a process in the cell nucleus that uses the DNA template to generate
precursors of messenger RNA molecules, which are then processed are exported to the cytoplasm, where the production of proteins takes place. Recently we have learned that posttranscriptional events also play a very significant role in the regulation of gene expression. In this project, we were elucidating the role of enzymes called poly(A) and poly(U) polymerases, which modify the 3’ end of mRNA by adding untemplated stretches of adenosine or uridine nucleotides. Such enzymes are known to influence the stability and translation of mRNAs. We have discovered a novel family of poly(A) polymerases, and our results strongly suggest that they contribute significantly to metazoan physiology and, more generally, that cytoplasmic polyadenylation plays a much broader role than previously anticipated. One of the members is an oncosuppressor of multiple myeloma a cancer of plasma cells.
Moreover, we discovered that poly(U) polymerases play an essential roll in defense against our genomic parasites, the retrotransposons LINE-1, which constitute about 17% of our genomes