Stefan Ameres

Mechanism and Biology of RNA Silencing

  • Small silencing RNAs regulate animal physiology and development, enhance target gene discovery in pharmacological industry and serve as next-generation therapy for human disease. In RNA silencing pathways, ~22 nucleotide small RNAs, such as microRNAs (miRNAs) and small interfering RNAs (siRNAs), guide ribonucleoprotein complexes to complementary sequences within messenger RNAs to mediate their post-transcriptional silencing.
    We are interested in molecular mechanisms that govern small RNA silencing pathways in flies and mammals. Our focus lies on processes that regulate the production of small RNAs, their assembly into ribonucleoprotein complexes, and the disassembly thereof in response to synthetic and natural triggers, such as target mRNAs. Our goal is to define the principles that establish and maintain small RNA profiles in a given tissue or cell type. To do so, we are using a combination of biochemical, genetic and bioinformatic approaches using Drosophila melanogaster as a model organism. The hypotheses emerging from our studies in flies are directly tested for their conservation in mammals.    

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    Stefan Ameres
    Group Leader
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Selected Publications

(2012)
 
Xie, J., Ameres, SL., Friedline, R., Hung, JH., Zhang, Y., Xie, Q., Zhong, L., Su, Q., He, R., Li, M., Li, H., Mu, X., Zhang, H., Broderick, JA., Kim, JK., Weng, Z., Flotte, TR., Zamore, PD., Gao, G. (2012). Long-term, efficient inhibition of microRNA function in mice using rAAV vectors. Nat Methods. 9(4):403-9 (abstract)
 
(2011)
 
Han, BW., Hung, JH., Weng, Z., Zamore, PD., Ameres, SL. (2011). The 3'-to-5' exoribonuclease Nibbler shapes the 3' ends of microRNAs bound to Drosophila Argonaute1. Curr Biol. 21(22):1878-87 (abstract)
 
(2010)
 
Ameres, SL., Horwich, MD., Hung, JH., Xu, J., Ghildiyal, M., Weng, Z., Zamore, PD. (2010). Target RNA-directed trimming and tailing of small silencing RNAs. Science. 328(5985):1534-9 (abstract)
 
(2008)
 
Tafer, H., Ameres, SL., Obernosterer, G., Gebeshuber, CA., Schroeder, R., Martinez, J., Hofacker, IL. (2008). The impact of target site accessibility on the design of effective siRNAs. Nat Biotechnol. 26(5):578-83 (abstract)
 
(2007)
 
Ameres, SL., Martinez, J., Schroeder, R. (2007). Molecular basis for target RNA recognition and cleavage by human RISC. Cell. 130(1):101-12 (abstract)
 


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