Zucchini consensus motifs determine the mechanism of pre-piRNA production

Izumi, Natsuko; Shoji, Keisuke; Suzuki, Yutaka; Katsuma, Susumu; Tomari, Yukihide

doi:10.1038/s41586-020-1966-9

Cited by 77 publications

(129 citation statements)

References 49 publications

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“…The endonuclease Zucchini (MitoPLD in the mouse) directed by Aub cleaves the piRNA precursor transcript generating the 3′ end of a new piRNA loaded into Aub. The rest of the piRNA precursor transcript is repeatedly bound at its 5′ end by Piwi and cleaved by Piwi-guided Zucchini, generating phased production of Piwi-loaded piRNAs toward the 3′ end of the piRNA precursor transcript [77][78][79][80][81]. While the phased piRNA production generates de novo piRNAs increasing piRNA diversity, the ping-pong amplification cycle increases the pool of pre-existing piRNAs.…”

Section: Box 1 Pirna Biogenesis and Function In Te Repressionmentioning

confidence: 99%

Functions of PIWI Proteins in Gene Regulation: New Arrows Added to the piRNA Quiver

Ramat

Simonelig

2021

Trends in Genetics

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Section: Box 1 Pirna Biogenesis and Function In Te Repressionmentioning

confidence: 99%

Functions of PIWI Proteins in Gene Regulation: New Arrows Added to the piRNA Quiver

Ramat

Simonelig

2021

Trends in Genetics

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“…In Drosophila, piRNA 3' end formation is largely dependent on the cleavage of pre-piRNAs by the endonuclease Zucchini (Zuc). Zuc uses a sequence motif to preferentially cleave upstream of uridine residues in vivo (35)(36)(37), hence, piRNAs generated by Zuc generally have sharp 3' ends and the nucleotide directly downstream of the 3' end tends to be a uridine (+1U bias) (8,9). We examined whether these characteristics were present in our previously generated small RNA deep sequencing libraries from Ae.…”

Section: Aedes Aegypti Pirnas Have Sharp 3' Endsmentioning

confidence: 99%

Endogenous piRNA-guided slicing triggers responder and trailer piRNA production from viral RNA inAedes aegyptimosquitoes

Joosten

Overheul

Rij

et al. 2020

Preprint

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ABSTRACTPIWI interacting (pi)RNAs are small RNAs mostly known to protect the genomes of animal germlines against transposable elements. In Drosophila, piRNA-mediated cleavage of transposon RNA triggers the release of a responder piRNAs via the ping-pong amplification cycle. Responder piRNA 3’ end formation by the endonuclease Zucchini is coupled to the production of downstream trailer piRNAs, expanding the repertoire of piRNAs that target transposons. Intriguingly, in Aedes aegypti mosquitoes, somatic piRNAs are produced from viral RNA, implying a role of viral (v)piRNAs in antiviral immunity. Knowledge on how vpiRNA 3’ ends are formed and whether viral RNA is subjected to trailer piRNA production, however, is lacking. To address these questions, we analyzed small RNA sequencing libraries from Ae. aegypti cells. We found that virus- and transposon-derived piRNAs have sharply defined 3’ ends, and that uridine residues are enriched directly downstream of dominant piRNA sequences, both of which are characteristic features of Zucchini-like cleavage of precursor piRNAs. Next, we designed a piRNA reporter system based on Sindbis virus recombinants that harbor target sites for abundant endogenous piRNAs. These piRNAs guide cleavage of the viral RNA, which is subsequently processed into abundant responder piRNAs. Using this reporter virus system, we identified the Ae. aegypti orthologs of Zucchini, which is required for sharp 3’ end formation of responder piRNAs, and Nibbler, a 3’-5’ exonuclease involved in the trimming of a subset of piRNAs and miRNAs. Furthermore, we found that cleavage of viral RNA triggers the production of trailer piRNAs, thus expanding the piRNA sequence pool that is able to target viral RNA. Our results have important implications for understanding how autonomous piRNA production from viral RNA can be triggered by just a few cleavage events by genome-encoded piRNAs.

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“…ZC3H12A, also known as MCPIP1 or Regnase-1, is a novel RNAbinding protein (RBP) that plays a key role in post-transcriptional regulation and immune homeostasis [50,51], a study shows that ZC3H12A is involved in circHECTD1/HECTD1-mediated macrophage activation in lung cancer [52]. PNLDC1 is a PARN-like 3'-to-5' exonuclease localized on the mitochondrial surface in mouse, Associated with the emergence of the mature piRNA [53]. TUDOR domain-containing proteins (TDRDs) are chie y responsible for recognizing methyl-lysine/arginine residue.…”

Section: Discussionmentioning

confidence: 99%

Construction of an RNA Binding Protein-based Model for Prognosis Prediction of Colorectal Cancer

Hui

Halike

et al. 2020

Preprint

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Background: Colorectalcancer (CRC) is a prevalent gastrointestinal tumor with high incidence and mortality. Dysregulation of RNA binding proteins (RBPs) has been found in a variety of cancers and is related to oncogenesis and progression. This study aimed to develop and validate new biomarkers related to CRC prognosis by a series of bioinformatics analysis.Methods: We mined the gene expression data of 510 CRC samples from The Cancer Genome Atlas (TCGA) database, differentially expressed genes were screened and prognosis-related genes were identified. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out. A prognosis-related gene signature was constructed by univariate and multivariate Cox analysis. Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curves were utilized to evaluate the signature,The test set was used to validate the RBPs risk score model.Survival analysis was carried out to determine the independent prognostic significance of the signature. A nomogram combined with the gene signature was constructed.Results: A total of 224 aberrantly expressed RBPs were obtained, comprising 78 downregulated and 146 upregulatedRBPs. 13 RBPs with p < 0.005 were revealed in univariateCox regression analysis of train group, then stepwise multivariate Cox regression was applied for constituting an eight- RBP (BRCA1, TERT, TDRD7, PPARGC1A, LUZP4, CELF4, ZC3H12C, PNLDC1) signature prognostic biomarkers. Further analysis demonstrated that high risk score for patients was significantly related to poor overall survival according to the model. The area under the time-dependent receiver operator characteristic curve of the prognostic model was 0.730 at 5 years. The signature-based risk score was an independent prognostic factor in CRC patients. We also established a nomogram based on eight RBPs and internal validation in the train set, which displayed a favorable discriminating ability for Colorectal cancer.Conclusions: The established eight-RBP signature may serve as a novel independent prognostic factor that could be an important tool to predict the prognostic outcome of CRC patients. However, the specific biological mechanism needs further verification.

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Zucchini consensus motifs determine the mechanism of pre-piRNA production

Cited by 77 publications

References 49 publications

Functions of PIWI Proteins in Gene Regulation: New Arrows Added to the piRNA Quiver

Functions of PIWI Proteins in Gene Regulation: New Arrows Added to the piRNA Quiver

Endogenous piRNA-guided slicing triggers responder and trailer piRNA production from viral RNA inAedes aegyptimosquitoes

Construction of an RNA Binding Protein-based Model for Prognosis Prediction of Colorectal Cancer

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