An essential role for PNLDC1 in piRNA 3′ end trimming and male fertility in mice

Zhang, Yue; Guo, Rui; Cui, Yiqiang; Zhu, Zhi-Ping; Zhang, Yingwen; Wu, Hao; Zheng, Bo; Yue, Qiuling; Bai, Shun; Zeng, Wentao; Guo, Xuejiang; Zhou, Zuomin; Shen, Bin; Zheng, Ke; Liu, Mingxi; Ye, Lan; Sha, Jiahao

doi:10.1038/cr.2017.125

Cited by 83 publications

(103 citation statements)

References 10 publications

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“…Two papers studying the function of PNLDC1 have been published during the revision of this paper . Their conclusions are essentially the same as those in our current study; namely, PNLDC1‐null mice showed the defects of piRNA 3′ end trimming, transposon gene silencing, and spermatogenesis.…”

Section: Resultssupporting

confidence: 83%

PNLDC 1, mouse pre‐pi RNA Trimmer, is required for meiotic and post‐meiotic male germ cell development

et al. 2018

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PIWI‐interacting RNAs (piRNAs) are germ cell‐specific small RNAs essential for retrotransposon gene silencing and male germ cell development. In piRNA biogenesis, the endonuclease MitoPLD/Zucchini cleaves long, single‐stranded RNAs to generate 5′ termini of precursor piRNAs (pre‐piRNAs) that are consecutively loaded into PIWI‐family proteins. Subsequently, these pre‐piRNAs are trimmed at their 3′‐end by an exonuclease called Trimmer. Recently, poly(A)‐specific ribonuclease‐like domain‐containing 1 (PNLDC1) was identified as the pre‐piRNA Trimmer in silkworms. However, the function of PNLDC1 in other species remains unknown. Here, we generate Pnldc1 mutant mice and analyze small RNAs in their testes. Our results demonstrate that mouse PNLDC1 functions in the trimming of both embryonic and post‐natal pre‐piRNAs. In addition, piRNA trimming defects in embryonic and post‐natal testes cause impaired DNA methylation and reduced MIWI expression, respectively. Phenotypically, both meiotic and post‐meiotic arrests are evident in the same individual Pnldc1 mutant mouse. The former and latter phenotypes are similar to those of MILI and MIWI mutant mice, respectively. Thus, PNLDC1‐mediated piRNA trimming is indispensable for the function of piRNAs throughout mouse spermatogenesis.

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Section: Resultssupporting

confidence: 83%

PNLDC 1, mouse pre‐pi RNA Trimmer, is required for meiotic and post‐meiotic male germ cell development

et al. 2018

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“…Furthermore, the structure of the CB is disrupted, and the localization of MIWI in the CB is lost but not for MILI and MVH in Tdrkh cKO round spermatids [62]. Mechanically, since Tdrkh itself does not contain any nuclease domain, its 3'-trimming might work through recruitment and cooperation with trimmer PNLDC1, which is pivotal for mammalian piRNA 3 -trimming and is essential for transposon silencing and spermatogenesis in mice [63][64][65].…”

Section: Tdrkh/tdrd2mentioning

confidence: 99%

“…Meanwhile, the processing of piRNA precursors into piRNA intermediates is also regulated by the conserved mitochondrial outer membrane protein MITOPLD, which is essential for primary piRNA biogenesis but not secondary piRNA biogenesis [29]. Additionally, as a conserved mitochondrial Tudor domain protein located in IMC, piP-body and MAM structures, TDRKH plays a vital role in piRNA 3' trimming via associating with the trimmer PNLDC1 during fetal piRNA biogenesis [63][64][65] and recruiting MIWI but not MILI to mitochondria in pachytene spermatocytes, therefore revealing that the mitochondria surface serves as a scaffolding for piRNA biogenesis [62].…”

Section: Primary Pirna Processingmentioning

confidence: 99%

Mitochondria Associated Germinal Structures in Spermatogenesis: piRNA Pathway Regulation and Beyond

Wang

Guo

et al. 2020

Cells

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Multiple specific granular structures are present in the cytoplasm of germ cells, termed nuage, which are electron-dense, non-membranous, close to mitochondria and/or nuclei, variant size yielding to different compartments harboring different components, including intermitochondrial cement (IMC), piP-body, and chromatoid body (CB). Since mitochondria exhibit different morphology and topographical arrangements to accommodate specific needs during spermatogenesis, the distribution of mitochondria-associated nuage is also dynamic. The most relevant nuage structure with mitochondria is IMC, also called pi-body, present in prospermatogonia, spermatogonia, and spermatocytes. IMC is primarily enriched with various Piwi-interacting RNA (piRNA) proteins and mainly functions as piRNA biogenesis, transposon silencing, mRNA translation, and mitochondria fusion. Importantly, our previous work reported that mitochondria-associated ER membranes (MAMs) are abundant in spermatogenic cells and contain many crucial proteins associated with the piRNA pathway. Provocatively, IMC functionally communicates with other nuage structures, such as piP-body, to perform its complex functions in spermatogenesis. Although little is known about the formation of both IMC and MAMs, its distinctive characters have attracted considerable attention. Here, we review the insights gained from studying the structural components of mitochondria-associated germinal structures, including IMC, CB, and MAMs, which are pivotal structures to ensure genome integrity and male fertility. We discuss the roles of the structural components in spermatogenesis and piRNA biogenesis, which provide new insights into mitochondria-associated germinal structures in germ cell development and male reproduction. Cells 2020, 9, 399 2 of 20Mitochondria-associated ER membranes (MAMs) are tight structural contacts, also named as MERCs (mitochondria-ER contacts);~20% of the mitochondrial surface are jointly opposing and contact directly with the ER, yielding to approximately 10 and 30 nm in distance [4,5]. MAMs participate in several cellular signaling pathways, including calcium transmission, phospholipid exchange, intracellular trafficking, autophagy, ER stress, mitochondrial biogenesis, and inflammasome formation. Disturbances to MAMs lead to neurodegenerative diseases and cancer [6,7]. Our previous work reported that MAMs are abundant in both human and mouse spermatogenic cells, and contain many crucial proteins that are associated with the Piwi-interacting RNA (piRNA) pathway [8]. However, the functions of MAMs are still mysterious in spermatogenesis.In this review, we review the insights gained from studying the structural components of mitochondria-associated germinal structures, including IMC, CB, and MAMs, which are pivotal structures to ensure genome integrity and male fertility. We summarize the ultra-structure of IMC and MAMs in mouse spermatocyte, as shown in Figure 1A. We also discuss the roles of the structural components in piRNA biogenesis and propose that further s...

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“…Three recent studies now show that PNLDC1 is required for piRNA 3′ end formation in mouse testis at different developmental stages. Nishimura et al , Ding et al , and Zhang et al independently revealed that PNLDC1 is required for 3′ end maturation for all (Mili‐, Miwi2‐, and Miwi‐bound) piRNAs.…”

Section: Pirna Biogenesis During Mouse Spermatogenesismentioning

confidence: 99%

“…However, the enzyme that is required for piRNA 3 0 end maturation in vertebrates remained enigmatic. Nishimura et al [1] in this issue of EMBO Reports and two independent studies [2,3] now identified PNLDC1 as the exonuclease that is responsible for piRNA 3 0 end processing and transposon silencing during mouse spermatogenesis. Together, these studies establish PNLDC1 as the piRNA 3 0 end trimmer in mouse.…”

Section: Alfred W Bronkhorst and René F Kettingmentioning

confidence: 99%

Trimming it short: PNLDC1 is required for piRNA maturation during mouse spermatogenesis

Bronkhorst

Ketting

2018

EMBO Reports

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Transposon silencing within the germ line requires the proper processing of piRNA intermediates. However, the enzyme that is required for piRNA 3′ end maturation in vertebrates remained enigmatic. Nishimura et al in this issue of EMBO Reports and two independent studies now identified PNLDC1 as the exonuclease that is responsible for piRNA 3′ end processing and transposon silencing during mouse spermatogenesis. Together, these studies establish PNLDC1 as the piRNA 3′ end trimmer in mouse.

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An essential role for PNLDC1 in piRNA 3′ end trimming and male fertility in mice

Cited by 83 publications

References 10 publications

PNLDC 1, mouse pre‐pi RNA Trimmer, is required for meiotic and post‐meiotic male germ cell development

PNLDC 1, mouse pre‐pi RNA Trimmer, is required for meiotic and post‐meiotic male germ cell development

Mitochondria Associated Germinal Structures in Spermatogenesis: piRNA Pathway Regulation and Beyond

Trimming it short: PNLDC1 is required for piRNA maturation during mouse spermatogenesis

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