A novel class of small RNAs bind to MILI protein in mouse testes

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Abstract
In RNA interference, small RNAs (siRNAs or miRNAs) act to regulate gene expression. They serve as specificity factors that direct the RISC (RNA-induced silencing) complex to the complementary mRNA targets. A major component of RISC is a protein of the Argonaute family. Two groups have now identified a new class of small RNAs that interact with one Argonaute subfamily, the Piwi class. These testis-specific small RNAs, called 'piRNAs', are slightly longer than the previously described small RNAs. The function of the piRNAs is not yet known, but they might be involved in sperm production. One of two studies that identifies a new class of small RNAs that interact with one Argonaute subfamily, the Piwi class. These testis-specific small RNAs, called 'piRNAs', are slightly longer than the previously described siRNAs and miRNAs. Small RNAs bound to Argonaute proteins recognize partially or fully complementary nucleic acid targets in diverse gene-silencing processes1,2,3,4. A subgroup of the Argonaute proteins—known as the ‘Piwi family’5—is required for germ- and stem-cell development in invertebrates6,7, and two Piwi members—MILI and MIWI—are essential for spermatogenesis in mouse8,9. Here we describe a new class of small RNAs that bind to MILI in mouse male germ cells, where they accumulate at the onset of meiosis. The sequences of the over 1,000 identified unique molecules share a strong preference for a 5′ uridine, but otherwise cannot be readily classified into sequence families. Genomic mapping of these small RNAs reveals a limited number of clusters, suggesting that these RNAs are processed from long primary transcripts. The small RNAs are 26–31 nucleotides (nt) in length—clearly distinct from the 21–23 nt of microRNAs (miRNAs) or short interfering RNAs (siRNAs)—and we refer to them as ‘Piwi-interacting RNAs’ or piRNAs. Orthologous human chromosomal regions also give rise to small RNAs with the characteristics of piRNAs, but the cloned sequences are distinct. The identification of this new class of small RNAs provides an important starting point to determine the molecular function of Piwi proteins in mammalian spermatogenesis.