“miRNAs and Alternative Polyadenylation”

Abstract:

MiRNAs are small regulatory RNAs that pair with 3’UTRs and repress mRNA translation. Because these recognition elements are degenerated, and small, miRNA targets are difficult to identify, thus the vast majority are still unknown.

Alternative Polyadenylation (APA) is an elusive process that produces genes with different mRNA 3’end isoforms. While it is routinely detected in normal states and altered in disease, its biological role in cells and tissues is still a mystery. APA allows genes to change their 3’UTR length and escape the negative regulation by miRNAs and RNA binding proteins. APA is achieved because of the presence of multiple polyadenylation signal (PAS) elements in the same 3’UTR, which are differentially recognized and cleaved by the RNA cleavage and polyadenylation complex. We still do not understand its exact composition, how it is assembled, how it recognizes the termination sequences on the pre-mRNAs, how it discriminates between multiple PAS elements, the role of each of the subunits, and the dynamics of how this process is executed in detail.

In this seminar, I will cover three short stories describing how miRNA regulatory networks evolved their target specificity, how they interface with APA and mechanistic insights on how APA is achieved in metazoans.