Gene regulation by micro-RNAs

Research

RNA interference (RNAi) is a conserved sequence-specific gene regulatory mechanism in animals and plants that is involved in transcriptional, post-transcriptional, and translational repression. It produces two types of regulatory RNA species i.e., small interfering RNAs (siRNAs) and micro RNAs (miRNAs).

miRNAs are an abundant class of tiny RNAs. They constitute ~1% of human genes and characteristically have regulatory functions. The known targets of the few miRNAs studied in detail and related bioinformatics data strongly suggest that miRNAs have important regulatory roles in development, cell cycle, and oncogenesis.

In spite of the fact that miRNAs represent an abundant RNA class, only a few miRNA targets have been identified so far. In addition, very little is known about how miRNAs regulate their targets, what proteins are associated with a particular miRNA, how these proteins are interacting and where miRNA-protein complexes are localized.

My laboratory uses biochemical and cell biology approaches to isolate and characterize miRNA associated proteins. Furthermore, we examine what proteins and what cellular processes are regulated by a specific miRNA in human cells and we dissect the mechanism of miRNA driven gene regulation using in vitro and in vivo methods.

Publications

Hain D, Bettencourt BR, Okamura K, Csorba T, Meyer W, Jin Z, Biggerstaff J, Siomi H, Hutvágner G, Lai EC, Welte M, Müller H-A. (2010) Natural Variation of the Amino-Terminal Glutamine-Rich Domain in Drosophila Argonaute2 Is Not Associated with Developmental Defects. PLoS ONE. 5(12): e15264

Monk CE, Hutvágner G, Arthur JSC. (2010) Regulation of miRNA Transcription in Macrophages in Response to Candida albicans. PLoS ONE. 5(10): e13669

Remenyi J, Hunter CJ, Cole C, Impey S, Monk CE, Martin KJ, Barton GJ, Hutvágner G, Arthur JSC. (2010) Regulation of the miR-212/132 locus by MSK and CREB in response to neurotrophins. Biochem J. 428(2): 281-91

JohnstonM, Geoffroy MC, Sobala A, Hay R, Hutvágner G. (2010) HSP90 Protein Stabilizes Unloaded Argonaute Complexes and Microscopic P-bodies in Human Cells. Mol Biol Cell. 21(9):1462-9

Gallagher IJ, Scheele C, Keller P, Nielsen AR, Remenyi J, Fischer CP, Roder K, Babraj J, Wahlestedt C, Hutvágner G, Pedersen BK, Timmons JA (2010) Integration of microRNA changes in vivo identifies novel molecular features of muscle insulin resistance in Type 2 Diabetes. Genome Medicine 2:9

Csorba T, Lózsa R, Hutvágner G, Burgyán J (2010) Polerovirus protein P0 prevents the assembly of small RNA containing RISC complexes and leads to degradation of ARGONAUTE1. Plant J. 62(3): 463-72

Cole C, Sobala A, Lu C, Thatcher SR, Bowman A, Brown JW, Green PJ, Barton GJ, Hutvágner G (2009) Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs. RNA. 15: 2147-2160

Mudhasani, R., Zhu, Z., Hutvagner, G., Eischen, C.M., Lyle, S., Hall, L.L., Lawrence, J.B., Imbalzano, A.N., Jones, S.N., (2008) Loss of miRNA biogenesis induces p19Arf-p53 signaling and senescence in primary cells. J Cell Biol. 181(7):1055-63. View Paper

Hutvagner, G., and Simard, M., (2008) Argonaute proteins: Key players in RNA silencing. Nat Rev Mol Cell Biol. (1):22-32.

Engels BM and Hutvagner G. (2006) Principles and effects of microRNA-mediated post-transcriptional gene regulation. Oncogene (46):6163-9

Hutvagner, G., (2005) Small RNA asymmetry in RNAi: function in RISC assembly and gene regulation. FEBS Lett. 579(26):5850-7.

Hutvagner, G., and Simard, M.J., (2005) RNA silencing: A journey into the RNA silencing world. Science309:1518

Hutvagner, G., Simard, M., Mello, C.G., and Zamore, P.D., (2004) Sequence-specific inhibition of small RNA function. PLoS Biology 2(4): 465-475.View Paper

Schwarz, D.S., Hutvagner, G., Du, T., Xu, Z., Aronin, N., Zamore, P.D., (2003) Asymmetry in the assembly of the RNAi enzyme complex. Cell115(2):199-208.

Schwarz, D.S., Hutvagner, G., Haley, B., Zamore, P.D., (2002) Evidence that siRNAs function as guides, not primers, in the Drosophila and human RNAi pathways. Mol Cell 10:537-548

Hutvagner, G., and Zamore, P.D., (2002) RNAi nature abhors a double-strand. Current Opin Genet Dev. 12(2):225-232.

Hutvagner, G., and Zamore, P.D., (2002) A microRNA in a multiple-turnover RNAi enzyme complex. Science 297:2056-2060. View Paper

Hutvagner, G., McLachlan, J., Pasquinelli, A., Bálint É., Tuschl T., and Zamore, P.D.,(2001) A Cellular Function for the RNA-Interference Enzyme Dicer in the Maturation of the let-7 Small Temporal RNA. Science 293:834-838.

Hutvagner, G., Mlynarova, and L., Nap, J.P., (2000) Detailed characterization of the post-transcriptional gene-silencing-related small RNA in a GUS gene silenced tobacco. RNA 6(10):1445-54.