Dr Gyorgy Hutvagner

Engels, B., Jannot, G., Remenyi, J., Simard, M.J. & Hutvagner, G.J. 2012, 'Polypyrimidine tract binding protein (hnRNP I) is possibly a conserved modulator of miRNA-mediated gene regulation.', PLoS One, vol. 7, no. 3.
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MiRNAs can regulate gene expression through versatile mechanisms that result in increased or decreased expression of the targeted mRNA and it could effect the expression of thousands of protein in a particular cell. An increasing body of evidence suggest that miRNAs action can be modulated by proteins that bind to the same 39UTRs that are targeted by miRNAs, suggesting that other factors apart from miRNAs and their target sites determine miRNA-modulation of gene expression. We applied an affinity purification protocol using biotinylated let-7 miRNA inhibitor to isolate proteins that are involved in let-7 mediated gene regulation that resulted in an affinity purification of Polypyrimidine Tract Binding protein (PTB). Here we show that PTB interacts with miRNAs and human Argonaute 2 (hAgo2) through RNA as well as identified potential mammalian cellular targets that are co-regulated by PTB and hAgo2. In addition, using genetic approach, we have demonstrated that PTB genetically interacts with Caenorhabditis elegans let-7 indicating a conserved role for PTB in miRNAmediated gene regulation.

Jannot, G., Bajan, S.M., GiguÞre, N., Bouasker, S., Banville, I.H., Piquet, S., Hutvagner, G.J. & Simard, M.J. 2011, 'The ribosomal protein RACK1 is required for microRNA function in both C. elegans and humans', EMBO Reports, vol. 12, no. 6, pp. 581-586.
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Despite the importance of microRNAs (miRNAs) in gene regulation, it is unclear how the miRNA-Argonaute complex-or miRNA-induced silencing complex (miRISC)-can regulate the translation of their targets in such diverse ways. We demonstrate here a direct in

Johnston, M. & Hutvagner, G.J. 2011, 'Post-translational modification of Argonautes and their role in small RNA mediated gene regulation', Silence: a Journal of RNA Regulation, vol. 2, no. 5, pp. 1-4.
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Shortly after their discovery, repertoires of miRNA were identified, together with proteins involved in their biogenesis and action. It is now obvious that miRNA-mediated gene regulation itself is regulated at multiple levels. Identifying the regulatory mechanisms that underpin small RNA homeostasis by modulation of their biogenesis and action has become a key issue, which can be partly resolved by identifying mediators of Argonautes turnover. An emerging theme in the control of Argonaute stability and activity is through posttranslational modifications, which are the focus of this review.

Moore, H.C., Johnston, M.B., Nicol, S.M., Bourdon, J., Thompson, A.M., Hutvagner, G.J. & Fuller-pace, F.V. 2011, 'An evolutionarily conserved, alternatively spliced, intron in the p68/DDX5 DEAD-box RNA helicase gene encodes a novel miRNA', Rna-A Publication Of The Rna Society, vol. 17, no. 4, pp. 555-562.
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The DEAD-box RNA helicase p68 (DDX5) plays important roles in several cellular processes, including transcription, pre-mRNA processing, and microRNA (miRNA) processing. p68 expression is growth and developmentally regulated, and alterations in p68 expres

Sobala, A. & Hutvagner, G.J. 2011, 'Transfer RNA-derived fragments: origins, processing, and functions', WIREs RNA, vol. 2, no. November/December, pp. 853-862.
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Deep sequencing approaches have revealed multiple types of small RNAs with known and unknown functions. In this review we focus on a recently identified group of smallRNAsthat are derived from transferRNAs(tRNAs), tRNAfragments (tRFs). We review the mechanism of their processing and their functions in mammalian cells, and highlight points of possible cross-talk between tRFs and the canonical small RNA pathway characterized by small interfering RNAs (siRNAs), microRNAs (miRNAs), and Piwi-interacting RNAs (piRNAs). We also propose a nomenclature that is based on their processing characteristics. ´ú® 2011 John Wiley & Sons, Ltd. WIREs RNA 2011 2 853Ô++862 DOI: 10.1002/wrna.96

Csorba, T., Lozsa, R., Hutvagner, G.J. & Burgyan, J. 2010, 'Polerovirus protein P0 prevents the assembly of small RNA-containing RISC complexes and leads to degradation of ARGONAUTE1', Plant Journal, vol. 62, no. 3, pp. 463-472.
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P>RNA silencing plays an important role in plants in defence against viruses. To overcome this defence, plant viruses encode suppressors of RNA silencing. The most common mode of silencing suppression is sequestration of double-stranded RNAs involved in

Hain, D., Bettencourt, B., Okamura, K., Csorba, T., Meyer, W., Jin, Z., Biggerstaff, J., Siomi, H., Hutvagner, G.J., Lai, E., Welte, M. & Muller, H. 2010, 'Natural Variation of the Amino-Terminal Glutamine-Rich Domain in Drosophila Argonaute2 Is Not Associated with Developmental Defects', PLoS ONE, vol. 5, no. 12, pp. 1-14.
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The Drosophila argonaute2 (ago2) gene plays a major role in siRNA mediated RNA silencing pathways. Unlike mammalian Argonaute proteins, the Drosophila protein has an unusual amino-terminal domain made up largely of multiple copies of glutamine-rich repea

Johnston, M.B., Geoffroy, M., Sobala, A., Hay, R. & Hutvagner, G.J. 2010, 'HSP90 Protein Stabilizes Unloaded Argonaute Complexes and Microscopic P-bodies in Human Cells', Molecular Biology Of The Cell, vol. 21, no. 9, pp. 1462-1469.
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Key components of the miRNA-mediated gene regulation pathway are localized in cytoplasmic processing bodies (P-bodies). Mounting evidence suggests that the presence of microscopic P-bodies are not always required for miRNA-mediated gene regulation. Here

Monk, C.E., Hutvagner, G.J. & Arthur, J.S. 2010, 'Regulation of miRNA Transcription in Macrophages in Response to Candida albicans', PLoS ONE, vol. 5, no. 10, pp. 1-12.
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Macrophages detect pathogens via pattern recognition receptors (PRRs), which trigger several intracellular signaling cascades including the MAPK and NFkB pathways. These in turn mediate the up-regulation of pro-inflammatory cytokines that are essential t

Remenyi, J., Hunter, C.J., Cole, C., Ando, H., Impey, S., Monk, C.E., Martin, K.J., Barton, G.J., Hutvagner, G.J. & Arthur, J.S. 2010, 'Regulation of the miR-212/132 locus by MSK1 and CREB in response to neurotrophins', Biochemical Journal, vol. 428, no. Part 2, pp. 281-291.
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Neurotrophins are growth factors that are important in neuronal development and survival as well as synapse formation and plasticity. Many of the effects of neurotrophins are mediated by changes in protein expression as a result of altered transcription

Cole, C., Sobala, A., Lu, C., Thatcher, S., Bowman, A., Brown, J., Green, P., Barton, G.J. & Hutvagner, G.J. 2009, 'Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs', RNA, vol. 15, no. 12, pp. 2147-2160.
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Deep sequencing technologies such as Illumina, SOLiD, and 454 platforms have become very powerful tools in discovering and quantifying small RNAs in diverse organisms. Sequencing small RNA fractions always identifies RNAs derived from abundant RNA specie

Hutvagner, G.J. & Simard, M.J. 2008, 'Argonaute proteins: key players in RNA silencing', Nature Reviews Molecular Cell Biology, vol. 9, no. 1, pp. 22-32.
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During the past decade, small non-coding RNAs have rapidly emerged as important contributors to gene regulation. To carry out their biological functions, these small RNAs require a unique class of proteins called Argonautes. The discovery and our compreh

Mudhasani, R., Zhu, Z., Hutvagner, G.J., Eischen, C., Lyle, S., Hall, L., Lawrence, J., Imbalzano, A. & Jones, S. 2008, 'Loss of miRNA biogenesis induces p19(Arf)-p53 signaling and senescence in primary cells', Journal Of Cell Biology, vol. 181, no. 7, pp. 1055-1063.
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Dicer, an enzyme involved in microRNA (miRNA) maturation, is required for proper cell differentiation and embryogenesis in mammals. Recent evidence indicates that Dicer and miRNA may also regulate tumorigenesis. To better characterize the role of miRNA i

Engels, B. & Hutvagner, G.J. 2006, 'Principles and effects of microRNA-mediated post-transcriptional gene regulation', Oncogene, vol. 25, no. 46, pp. 6163-6169.
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MicroRNAs (miRNAs) are abundant regulatory RNAs involved in the regulation of many key biological processes. Recent advances in understanding the mechanism of RNA interference and miRNA-mediated mechanisms shed light on major principals of the formation

Hutvagner, G.J. 2005, 'Small RNA asymmetry in RNAi: Function in RISC assembly and gene regulation', FEB Letters, vol. 579, no. 26, pp. 5850-5857.
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RNAi is a conserved gene-specific regulatory mechanism, which silences target gene expression transcriptionally and post-transcriptionally. The RNAi machinery converts the sequence specific information of a long double stranded RNAs (dsRNAs) into small 2

Hutvagner, G.J., Simard, M.J., Mello, C. & Zamore, P. 2004, 'Sequence-specific inhibition of small RNA function', Plos Biology, vol. 2, no. 4, pp. 465-475.
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Hundreds of microRNAs (miRNAs) and endogenous small interfering RNAs (siRNAs) have been identified from both plants and animals, yet little is known about their biochemical modes of action or biological functions. Here we report that 2'-O-methyl oligonuc