Non-coding RNAs

Research on non-coding RNAs is at heart of our lab. We study the biogenesis and function of a plethora of different classes of short and long ncRNAs in a wide range of organisms. We also continue to apply our knowledge gained from these studies to develop and improve innovative RNA silencing tools for cancer research and other areas of the lab.

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Expression of Piwi-Family Members in Drosophila ovaries. Adapted from Brennecke et al. (2007) Cell

From early studies on the molecular mechanism of gene silencing via small interfering RNAs (siRNAs), to microRNAs and their associated Argonaute protein partners, we have learned a great deal from biochemical and structural approaches. In the past years, we have become very interested in a class of small RNAs that specifically operates in animal gonads. This conserved small RNA silencing system, known as the piRNA pathway, provides an elegant defense mechanism that protects the genetic information of animal germ cells from the deleterious effects of molecular parasites known as transposable elements. At the core of the piRNA pathway lies a complex of Piwi-clade Argonaute proteins and their associated 24- to 32-nt RNA binding partners, the Piwi-interacting RNAs (piRNAs). In Drosophila, piRNAs typically originate from acute transposon mobilization events and from piRNA clusters, which provide a genomic memory of ancestral transposon activity, through the coordinated activity of several processing factors. Mouse piRNAs share many features with their fly counterparts, but also show unique features (like the lack of sequence homology to transposons). Using mouse models and Drosophila as model organisms, work in the lab aims to uncover the molecular mechanism that converts transposon and cluster transcripts – but not coding mRNAs – into mature piRNAs and to study the endogenous functions of this fascinating class of small RNAs.

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Some reported effects of lncRNAs at the chromatin level. Reviewed in Sabin et al. (2012) Molecular Cell

Long non-coding RNAs (lncRNAs) have recently emerged as major contributor to cellular RNA pools, yet examples with defined functions remain sparse. We have set out to systematically address the roles of lncRNAs in Drosophila and mouse models. As first steps towards this goal, we have built a consensus repertoire of the lncRNAs expressed in our system and the necessary tools to disrupt their expression. Using the mouse hematopoietic lineage as a model, we study the role that these transcripts play in stem cell self-renewal, differentiation and disease.