Riding in silence: a little snowboarding, a lot of small RNAs

From 14 to 19 January 2010, small RNAs once again attracted the attention of more than 500 attendees to symposium on RNA silencing: Mechanism, Biology and Applications, held in Keystone, Colorado. In the midst of the breathtaking panorama of the Rocky Mountain summits, exciting and rapidly evolving science mixed with superb riding and skiing created a stimulating atmosphere for discussions on the mechanisms, biology and applications of RNA silencing.A much-discussed topic at the meeting was the mechanisms and regulation of micro (mi)RNA biogenesis. In her keynote address, Narry Kim (Seoul National University) elaborated on the effect of pre-miRNA uridylation. She reported that the terminal uridylyl transferase, TUT4, acts on the 3' termini of pre-miRNAs to suppress pre-miRNA processing [1,2]. Although this process requires the scaffold protein Lin-28 to recruit the TUTase to specific pre-miRNAs, uridylation is not limited to these pre-miRNAs. Whereas oligo-uridylylation inhibits pre-miRNA dicing, mono-uridylylation can enhance pre-miRNA processing by human and fly Dicer proteins in vitro, suggesting that post-transcriptional pre-miRNA modification can have a versatile effect on processing. Surprisingly, the addition of one or a few additional nucleotides to the 3' end of a pre-miRNA did not alter the 3' end of the miRNA excised from the 5' side of the stem. To explain these data, Kim proposed an alternative model to the PAZ-anchored molecular ruler model that emerged from the structure of Giardia Dicer [3]. She suggested that Dicer proteins in higher eukaryotes measure mainly from the 5' end of a pre-miRNA, rather than from its 3' end.Jennifer Doudna (University of California, Berkeley) described the first structural insights into human pre-miRNA processing and loading by electron microscopy [4]. She presented biochemical cross-linking studies employing a recombinant human Dicer-TRBP (trans activation response RNA binding protein) complex. These data suggest that th