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Dr. Ingo Büssing:"A novel nuclear export route for miRNAs?"

What Lecture
When 02.04.2009
from 15:30 to 16:30
Where Seminar Room ZBSA, basement
Contact Name Dr. Esther Dalfó Capella
Contact Email
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Dr. Ingo Büssing
Friedrich Miescher Institute (FMI) for Biomedical Research, Basel

 

A novel nuclear export route for miRNAs?

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate numerous target genes to control major developmental pathways. The biogenesis of miRNAs has been investigated extensively leading to the following model: MiRNAs are transcribed by the RNA polymerase II from dedicated genetic loci, yielding a primary transcript that is polyadenylated and capped.

The nuclear RNase Drosha cleaves the pri-miRNA to generate the precursor miRNA (premiRNA) of about ~70 nucleotides. In flies and vertebrates, the pre-miRNA is then recognized and exported to the cytoplasm by the importin-â family member Exportin-5. Cytoplasmic processing into the mature miRNA of ~22 nucleotides is mediated by the Dicer RNase. However, C. elegans lacks an Exportin-5 orthologue, and we tested other members of the importin-â family for their function in miRNA biogenesis.

I will present an alternative nuclear export route that is used in C.elegans. This novel pathway involves the Crm1/Xpo1 orthologue and the cap-binding complex (CBC), composed of CBP20 and CBP80, and appears to use a distinct miRNA precursor as export substrate. Genetic analysis and developmental phenotypes show that this pathway is essential for C. elegans miRNA biogenesis. The findings support that C. elegans miRNA biogenesis substantially deviates from the canonical biogenesis pathway. Moreover, the different biogenesis pathway might provide an explanation for the alternative genomic organization of miRNA loci in C.elegans.