Piwi Nuclear Localization and Its Regulatory Mechanism in Drosophila Ovarian Somatic Cells

Abstract

In Drosophila ovarian somatic cells (OSCs), Piwi represses transposons transcriptionally to maintain genome integrity. Piwi nuclear localization requires the N terminus and PIWI-interacting RNA (piRNA) loading of Piwi. However, the underlying mechanism remains unknown. Here, we show that Importinα (Impα) plays a pivotal role in Piwi nuclear localization and that Piwi has a bipartite nuclear localization signal (NLS). Impα2 and Impα3 are highly expressed in OSCs, whereas Impα1 is the least expressed. Loss of Impα2 or Impα3 forces Piwi to be cytoplasmic, which is rectified by overexpression of any Impα members. Extension of Piwi-NLS with an additional Piwi-NLS leads Piwi to be imported to the nucleus in a piRNA-independent manner, whereas replacement of Piwi-NLS with SV40-NLS fails. Limited proteolysis analysis suggests that piRNA loading onto Piwi triggers conformational change, exposing the N terminus to the environment. These results suggest that Piwi autoregulates its nuclear localization by exposing the NLS to Impα upon piRNA loading.

Gastric juice piR‐1245: A promising prognostic biomarker for gastric cancer

“…18 Recent reports demonstrated that piRNAs were of great importance for carcinogenesis. 7,9 It was also active in various cancer cells, implying that somatic cancer stem cells might adopt an unlimited proliferation potency via piRNA alteration. 30 Zhang et al showed that piR-651 was responsible for tumorigenesis of non-small cell lung cancer by inhibiting its malignant behavior.…”

“…8 Aberrant expression of piRNA is a key character with feasible implications for diagnosis or prognosis in multiple types of cancers. 9 Besides, gastric juice (GJ) can provide useful information and has diagnostic value in GC. [10][11][12] Prominently, piRNAs have been disclosed to be present in a stable form in human body fluids, including the plasma and serum.…”

Armitage determines Piwi−piRISC processing from precursor formation and quality control to inter‐organelle translocation

“…Expression vector of Armi-Flag WT was produced by inverse PCR and infusion using the RNAi-resistant Flag-Armi WT vector [31] as a template. Expression vectors of Flag-tagged Piwi mutants (PAZmt and MIDmt) were generated by inverse PCR and infusion, using the RNAi-resistant Myc-Piwi PAZmt vector [24] and the RNAi-resistant Flag-Piwi WT vector [13] as templates, respectively. Armi-Flag means that a Flag peptide was added to the Cterminal end of Armi.…”

“…Therefore, by their nature, flam-derived piRNAs are created to act as antisense oligonucleotides to silence their parental transposons. The complex is then imported into the nucleus and represses transposons at the transcriptional level [12,13]. The Piwi-piRISC assembly takes place in the cytoplasm.…”

“…The Piwi-piRISC assembly takes place in the cytoplasm. The complex is then imported into the nucleus and represses transposons at the transcriptional level [12,13].…”