Sorting of Drosophila small silencing RNAs partitions microRNA* strands into the RNA interference pathway

In some cases, both arms of the miRNA duplex give rise to functional mature miRNAs that are loaded into Argonaute proteins to regulate gene expression.

“However, in some cases, both arms of the duplex give rise to functional mature miRNAs that are loaded into Argonaute proteins to regulate gene expression (Ghildiyal, Xu, Seitz, Weng, & Zamore, 2009; Okamura, Liu, & Lai, 2009).”

The most commonly observed 5' nucleotide of miRNA guide strands is Uracil, whereas the passenger strand often begins with Cytosine at the 5' end.

“Consistently, the most commonly observed 5′ nucleotide of miRNA guide strands is a Uracil, whereas the passenger strand often begins with a Cytosine at the 5′ end (Ghildiyal et al., 2009; Mi et al., 2008; Takeda, Iwasaki, Watanabe, Utsumi, & Watanabe, 2008; Warf, Johnson, & Bass, 2011; Figure 2c).”

In fly ovaries, the miR-92a-3p, miR-988-3p, and miR-284-5p strands are expressed at higher levels than their corresponding passenger strands, while the miR-92a-5p, miR-988-5p, and miR-284-3p strands are expressed in excess within fly heads.

“In fly ovaries, the miR‐92a‐3p, miR‐988‐3p, and miR‐284‐5p strands are expressed at higher levels than their corresponding passenger strands, while the miR‐92a‐5p, miR‐988‐5p, and miR‐284‐3p strands are expressed in excess within fly heads (Ghildiyal et al., 2009).”

Similar observations have been reported in flies, where several miRNA duplexes were found to exhibit tissue-specific differences in miRNA strand selection.

“Similar observations have been reported in flies, where several miRNA duplexes were found to exhibit tissue‐specific differences in miRNA strand selection (Ghildiyal et al., 2009).”

While often supported by in vivo observations, how well the rules of miRNA strand selection hold up in a living organism throughout its lifespan is yet to be established.

“While often supported by in vivo observations, such as the observation that most miRNAs begin with a 5′ Uracil (Ghildiyal et al., 2009; Mi et al., 2008; Takeda et al., 2008; Warf et al., 2011), how well these rules hold up in a living organism throughout its lifespan is yet to be established.”