Biochemical analysis of microRNA biogenesis in Drosophila melanogaster

• Applicant: Professor Dr. Klaus Förstemann
• Subject Area: Cell Biology
• Term: from 2008 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 68032184

MicroRNAs (miRNAs) are small, cellular nucleic acids that – like siRNAs - control gene activity post-transcriptionally. Together with a specific set of effector proteins, target messenger RNAs are recog-nized through the partial complementarity between miRNA and messenger RNA. This leads to transla-tional repression and/or increased turnover of this mRNA. The incorporation of a miRNA into its effec-tor protein of the Argonaute-family is of particular importance: In this step, a certain biochemical activity (contributed by the Argonaute-protein) is associated with a specific targeting sequence. Understandably, the choice of a specific effector protein for a given miRNA is not random but tightly controlled by so-called loading complexes which interpret the structure of a certain miRNA biogenesis intermediate. The goal of the proposed research is to describe the sorting of miRNAs into the available effector proteins and the biological significance of this phenomenon. We will examine who recognizes the structure of mi/siRNA biogenesis intermediates, through which mechanism the recognition of a specific RNA structure leads to an asymmetric distribution into the effector proteins and how the organism responds to impaired sorting.

• DFG Programme: Research Grants