Speaker: Jon van der Oost, Laboratory of Microbiology, Wageningen University

RNA and DNA interference in prokaryotes

RNA interference is an important pathway that generally is responsible for control of gene expression in Eukaryotes. In some cases the system RNAi is used as defence system against invading viruses. The key protein of the RNAi system is the Argonaute nuclease that uses small RNA molecules as guides to recognize complementary RNA targets, i.e. RNA-guided RNA interference. In 2005, a distinct interference system has been discovered in bacteria and archaea. This CRISPR-Cas system uses small CRISPR RNA guides to target complementary DNA, i.e. RNA-guided DNA interference [1]. The CRISPR-Cas system is an heritable adaptive immune system, providing resistance against invading mobile genetic elements. Whereas most CRISPR systems target complementary DNA, one CRISPR variant has been demonstrated to targets RNA [2,3]. Many CRISPR systems rely on large multi-subunit ribonucleoprotein complexes (Cascade), however, in the Cas9-type system the CRISP RNA guide is associated with a single, multi-domain protein [2]. Elucidation of the molecular mechanism of the Cas9 system have allowed for spectacular developments towards genome editing applications [4]. In addition to the CRISPR system, recently also Argonaute-based defence systems have been described for bacteria. The Argonaute of Thermus thermophilus acquires small DNA guides that allow for nicking of complementary DNA sequences, i.e. DNA-guided DNA
nterference [5]. This seminar will describe differences and similarities of these novel prokaryotic interference systems.

[1]        Brouns et al. (2008) Science 321, 960-964

[2]        Makarova et al. (2011) Nat Rev Microbiol 9, 467-477

[3]        Staals et al. (2013) Mol Cell 52, 135-145

[4]        Van der Oost (2013) Science 339, 768-770

[5]        Swarts et al. (2014) Nature 507, 258-261