Structural basis for microRNA targeting

MicroRNAs (miRNAs) control expression of thousands of genes in plants and animals. miRNAs function by guiding Argonaute proteins to complementary sites in messenger RNAs (mRNAs) targeted for repression. We determined crystal structures of human Argonaute-2 (Ago2) bound to a defined guide RNA with and without target RNAs representing miRNA recognition sites. These structures suggest a stepwise mechanism, in which Ago2 primarily exposes guide nucleotides (nt) 2 to 5 for initial target pairing. Pairing to nt 2 to 5 promotes conformational changes that expose nt 2 to 8 and 13 to 16 for further target recognition. Interactions with the guide-target minor groove allow Ago2 to interrogate target RNAs in a…

• UD
  U.S. Department of Energy

  Awards: AC02-06CH11357, P41 GM103403, DE-AC02, 06CH11357, DE-AC02-06CH11357, DE-AC02-
• AH
  American Heart Association
• NI
  National Institutes of Health

  Awards: GM104475, P41 GM103403, GM103403, DE-AC02-06CH11357, R01 GM104475
• NI
  National Institute of General Medical Sciences

  Awards: GM104475, DE-AC02-06CH11357, GM103403, P41 GM103403