piR_015520 Belongs to Piwi-Associated RNAs Regulates Expression of the Human Melatonin Receptor 1A Gene

Abstract

Piwi-associated RNAs (piRNAs) are a distinct class of 24- to 30-nucleotide-long RNAs produced by a Dicer-independent mechanism, and are associated with Piwi-class Argonaute proteins. In contrast to the several hundred species of microRNAs (miRNAs) identified thus far, piRNAs consist of more than 30,000 different species in humans. Studies in flies, fish and mice implicate these piRNAs in regulating germ line development, the silencing of selfish DNA elements, and maintaining germ line DNA integrity. Most piRNAs map to unique sites in the human genome, including intergenic, intronic, and exonic sequences. However, the role of piRNAs in humans remains to be elucidated. Here, we uncover an unexpected function of the piRNA pathway in humans. We show for the first time, that the piRNA_015520, located in intron 1 of the human Melatonin receptor 1A (MTNR1A) gene, is expressed in adult human tissues (testes and brain) and in the human cell line HEK 293. Although the role of piR_015520 expression in brain tissue remains unknown, the testes-specific expression is consistent with previous findings in several species.Surprisingly, in contrast to the mechanism known for miRNA-mediated modulation of gene expression, piRNA_015520 negatively regulates MTNR1A gene expression by binding to its genomic region. This finding suggests that changes in individual piRNA levels could influence both autoregulatory gene expression and the expression of the gene in which the piRNA is located. These findings offer a new perspective for piRNAs functioning as gene regulators in humans.

Emerging roles for PIWI proteins in cancer

“…piRNAs are highly expressed in reproductive tissues, but are also expressed in the brain [95], and a normal human plasmaderived exosome had 1.31% piRNAs [96]. Some piRNAs can be associated with HIWI2 in somatic cells including cancer cells [97].…”

PIWI Proteins and PIWI-Interacting RNA: Emerging Roles in Cancer

“…For example, piR_015520 is in intron 1 of the human melatonin receptor 1A gene (MTNR1A) gene, which has an altered expression in prostate cancer cells. piR_015520 has been shown negatively regulated MTNR1A gene expression by binding to its genomic region and overexpression of piR_015520 lead to a repression of MTNR1A expression in a concentration-dependent manner [53]. This data manifests that piRNA expression level alterations could influence the expression level of the gene where the piRNA is located, providing a novel insight of piRNAs as gene regulators in humans.…”

“…Transposons silencing of piRNAs by DNA methylation could lead to transcriptional gene silencing. For instance, in the central nervous system (CNS) and other somatic tissues in Aplysia , piRNAs could induce CpG methylation and transcriptional silencing of a key plasticity related gene, CREB2 [53]. …”

773 Piwi-interacting RNAs as novel prognostic markers in clear cell renal cell carcinomas

“…The curves from 76 non-metastatic and 30 metastatic patients listed in Table 1 are presented according to (a) pathological stage, (b) grading, and expression of (c) piR-30924, (d) piR-57125, (e) piR-38756, and (f) combination of all three piRNAs. The log-rank test was used to confirm significant differences between the survival probabilities genes [23,45]. The identification of piRNA targets is one of the key challenges in our understanding of the function of this class of small non-coding RNAs.…”