In 2008, Place et al. identified targets for miRNA miR-373 on the promoters of several human genes and found that introduction of miR-373 mimics into human cells induced the expression of its predicted target genes. This study provided the first example that RNAa could be mediated by naturally occurring non-coding RNA (ncRNA). In 2011, Huang et al. further demonstrated in mouse cells that endogenous RNAa mediated by miRNAs functions in a physiological context and is possibly exploited by cancer cells to gain a growth advantage. Since then, a number of miRNAs have been shown to upregulate gene expression by targeting gene promoters  or enhancers, thereby, exerting important biological roles. A good example is miR-551b-3p which is overexpressed in ovarian cancer due to amplification. By targeting the promoter of STAT3 to increase its transcription, miR-551b-3p confers to ovarian cancer cells resistance to apoptosis and a proliferative advantage.
In C. elegans hypodermal seam cells, the transcription of lin-4 miRNA is positively regulated by lin-4 itself which binds to a conserved lin-4 complementary element in its promoter, constituting a positive autoregulatory loop.
In C. elegans, Argonaute CSR-1 interacts with 22G small RNAs derived from RNA-dependent RNA polymerase and antisense to germline-expressed transcripts to protect these mRNAs from Piwi-piRNA mediated silencing via promoting epigenetic activation.
It is currently unknown how widespread gene regulation by endogenous RNAa is in mammalian cells. Studies have shown that both miRNAs  and Ago proteins (Ago1)  bind to numerous sites in human genome, especially promoter regions, to exert a largely positive effect on gene transcription.