PhD defense: Laura Arribas

Post-transcriptional gene regulation mediated by small RNAs and ARGONAUTE1 in Arabidopsi

Supervisor
Peter Brodersen, Associate Professor, University of Copenhagen

Exam Committee
Geneviève Thon, Associate Professor , Functional Genomics, University of Copenhagen
Lionel Navarro, Research Scientist and group leader, Ecole Normale Supérieure de Paris
Torben Heick-Jensen, Professor, Aarhus University

Abstract
RNA silencing is an ancient mechanism with fundamental roles in regulation of gene expression and defence against viruses and transposable elements. Silencing pathways act via 20-30 nt small RNAs that guide Argonaute (AGO) proteins to complementary mRNA targets for repression. One possible outcome of RNA silencing is post-transcriptional regulation that is brought about by AGO through endonucleolytic cleavage (slicing), translational inhibition, or RNA decay.
In plants, AGO1 regulates endogenous genes via slicing and translational repression, although it remains unclear whether slicing-independent RNA decay also plays a role. Several other aspects of AGO1-mediated silencing are unknown, including the molecular mechanisms underlying translational repression, how slicing is avoided to allow translational inhibition to take place, and whether the different modes of target mRNA repression have distinct biological roles. To address these questions, we generated Arabidopsis ago1 mutants deficient in either slicing or recruitment of partners that could potentially mediate translational repression. Through molecular and phenotypic characterization of the mutants as well as biochemical analyses of purified AGO1 protein, we provide new mechanistic insights into post-transcriptional gene regulation mediated by small RNAs and AGO1 in plants.