Protein-RNA Recognition Events in RNA Interference
Dinshaw J. Patel
Structural Biology Program
Memorial Sloan-Kettering Cancer Center
New York, NY, 10021, USA
RNA interference (RNAi) and related processes use short RNAs to mediate gene regulation. A key component is short interfering RNA (siRNA), composed of an ≈ 19 bp duplex containing 5'-phosphate and 2-nt 3'-overhangs. Our group has solved the crystal structures of two protein-siRNA complexes that address key issues related to siRNA recognition. The first complex involves the p19 protein, encoded by the tombusvirus, which targets plant siRNAs, and suppresses the RNAi-mediated anti-viral response. This complex elucidates aspects of siRNA duplex length recognition and their functional implications [1]. The second complex involves the PAZ domain, found in Dicer and Argonaute proteins, bound to siRNA. This complex elucidates aspects of siRNA end recognition and their functional implications [2]. More recently, we have solved the crystal structure of the 704-aa Aquifex aeolicus Argonaute protein containing PAZ, PIWI, two other domains and two linker segments, which provides insights into models of mRNA alignment and site-specific cleavage in the RNA induced silencing complex.
[1] Ye, K., Malinina, L. & Patel, D. J. (2003). Recognition of small interfering RNA by a viral suppressor of RNA silencing. Nature 426, 874-878.
[2] Ma, J-B., Ye, K. & Patel, D. J., (2004). Crystal structure of PAZ-small interfering RNA complex. Nature 429, 318-322.
Back to NMR: Application to Structural Genomics I
Back to The 56th Southeast Regional Meeting 2004 (November 10-13, 2004)