JVI Accepts, published online ahead of print on 7 October 2009

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J. Virol. doi:10.1128/JVI.01325-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Characterization of viral and human RNAs smaller than canonical microRNAs

Zhihua Li, Sang Woo Kim, Yuefeng Lin, Patrick S. Moore, Yuan Chang, and Bino John

University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA; Molecular Virology Program, Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, PA 15213, USA

Recently identified small (20 to 40 bases) RNAs such as microRNAs (miRNAs) and endogenous siRNAs participate in important cellular pathways. In this report, we systematically characterize several novel features of human and viral RNA products smaller than miRNAs. We find that Kaposi sarcoma-associated herpesvirus K12-1 miRNA (23 bases), associates with a distinct, unusually small (17 bases) RNA (usRNA) that can effectively downregulate a K12-1 miRNA target, human RAD21, suggesting that stable degradation-like products may also contribute to gene regulation. High-throughput sequencing reveals a diverse set of human miRNA-derived usRNAs and other non-miRNA-derived usRNAs. Human miRNA-derived usRNAs preferentially match to 5' ends of miRNAs, and are also more likely to associate with the siRNA effector protein Ago2, than Ago1. Many non-miRNA-derived usRNAs associate with Ago proteins and also frequently contain C-rich 3'-specific motifs that are overrepresented in comparison to piRNAs and TSSa-RNAs. We postulate that approximately 30% of usRNAs could have evolved to participate in biological processes including gene-silencing.