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Retrotransposition & regulatory RNAs

Oliver Weichenrieder

Oliver Weichenrieder

  • PhD at EMBL, Grenoble, 1999
  • Postdoc and Research Associate, Netherlands Cancer Institute, Amsterdam, 2000-06
  • Project leader at the MPI since 2006

Research Interest

Many cellular processes are regulated at the RNA level. We are interested in the molecular and structural details that govern the fate of RNA molecules in the cell. We work on RNA retrotransposition, translational repression and regulated RNA degradation. To this aim we use X-ray crystallography in combination with biochemical approaches and various assays both in vitro and in vivo. Current research spins around three topics.

First, we investigate the molecular mechanisms underlying the mobility of retrotransposons in the human genome. These apparent molecular parasites currently account for 25 % of our genomic DNA sequence in the form of LINE-1 and Alu elements. Their impact on human evolution and disease is just beginning to be analyzed in greater detail. Our current work involves the reconstitution of higher order LINE-1 and Alu ribonucleoprotein particles for structural and functional studies.

Second, we structurally dissect the eukaryotic mRNA 5’ decapping machinery to understand the role(s) of the individual protein components in the crucial regulation of mRNA turnover. Our recent crystal structures reveal a previously unknown connectivity and complexity of the mRNA decapping network in multicellular eukaryotes.

Third, we also look at the post-transcriptional regulation of RNA in prokaryotes, in particular at small cis-acting ligand-binding RNAs (riboswitches) and trans-acting small RNAs (sRNAs) that bind the bacterial Sm-like protein Hfq.

Selected Reading

Khazina E, Truffault V, Büttner R, Schmidt S, Coles M, Weichenrieder O. (2011) Trimeric structure and flexibility of the L1ORF1 protein in human L1 retrotransposition. Nat Struct Mol Biol 18, 1006-14.

Boland A, Huntzinger E, Schmidt S, Izaurralde E, Weichenrieder O. (2011) Crystal structure of the MID-PIWI lobe of a eukaryotic Argonaute protein. Proc Natl Acad Sci USA 108, 10466- 71.

Sauer E, Weichenrieder O. (2011) Structural basis for RNA 3‘-end recognition by Hfq. Proc Natl Acad Sci USA 108, 13065-70.
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The human LINE-1 element and its retrotransposition cycle.
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Crystal structure of the LINE-1 ORF1 protein trimer.