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

Bronkhorst, Alfred W; Ketting, René F.

doi:10.15252/embr.201845824

Cited by 10 publications

(15 citation statements)

References 12 publications

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“…The extent to which the regulation of PCD might still be relevant to eTudor and piRNA function, despite the loss of the DCD domain, remains to be elucidated, but there is evidence suggesting that it could be considerable. In the light of the putative evolutionary connection between the ancient form of PCD and the evolution of the eTudors and the piRNA network, it seems more explicable that conserved piRNA biogenesis factors Tudor-KH and MitoPLD/Zucchini are mitochondrially localized, perinuclear piRNA processing germ granules are also closely associated with mitochondria in addition to nuclear pores, and that reported phenotypes of many piRNA factor mutants include induction of PCD and/or germline mortality [ 75 , 140 – 144 ]. PCD is an important part of tissue differentiation, and piRNAs can prevent ectopic expression of somatic genes that might contribute to PCD or senescence of the germline [ 145 , 146 ].…”

Section: Discussionmentioning

confidence: 99%

Modified base-binding EVE and DCD domains: striking diversity of genomic contexts in prokaryotes and predicted involvement in a variety of cellular processes

2020

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Background DNA and RNA of all cellular life forms and many viruses contain an expansive repertoire of modified bases. The modified bases play diverse biological roles that include both regulation of transcription and translation, and protection against restriction endonucleases and antibiotics. Modified bases are often recognized by dedicated protein domains. However, the elaborate networks of interactions and processes mediated by modified bases are far from being completely understood. Results We present a comprehensive census and classification of EVE domains that belong to the PUA/ASCH domain superfamily and bind various modified bases in DNA and RNA. We employ the “guilt by association” approach to make functional inferences from comparative analysis of bacterial and archaeal genomes, based on the distribution and associations of EVE domains in (predicted) operons and functional networks of genes. Prokaryotes encode two classes of EVE domain proteins, slow-evolving and fast-evolving ones. Slow-evolving EVE domains in α-proteobacteria are embedded in conserved operons, potentially involved in coupling between translation and respiration, cytochrome c biogenesis in particular, via binding 5-methylcytosine in tRNAs. In β- and γ-proteobacteria, the conserved associations implicate the EVE domains in the coordination of cell division, biofilm formation, and global transcriptional regulation by non-coding 6S small RNAs, which are potentially modified and bound by the EVE domains. In eukaryotes, the EVE domain-containing THYN1-like proteins have been reported to inhibit PCD and regulate the cell cycle, potentially, via binding 5-methylcytosine and its derivatives in DNA and/or RNA. We hypothesize that the link between PCD and cytochrome c was inherited from the α-proteobacterial and proto-mitochondrial endosymbiont and, unexpectedly, could involve modified base recognition by EVE domains. Fast-evolving EVE domains are typically embedded in defense contexts, including toxin-antitoxin modules and type IV restriction systems, suggesting roles in the recognition of modified bases in invading DNA molecules and targeting them for restriction. We additionally identified EVE-like prokaryotic Development and Cell Death (DCD) domains that are also implicated in defense functions including PCD. This function was inherited by eukaryotes, but in animals, the DCD proteins apparently were displaced by the extended Tudor family proteins, whose partnership with Piwi-related Argonautes became the centerpiece of the Piwi-interacting RNA (piRNA) system. Conclusions Recognition of modified bases in DNA and RNA by EVE-like domains appears to be an important, but until now, under-appreciated, common denominator in a variety of processes including PCD, cell cycle control, antivirus immunity, stress response, and germline development in animals.

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Section: Discussionmentioning

confidence: 99%

Modified base-binding EVE and DCD domains: striking diversity of genomic contexts in prokaryotes and predicted involvement in a variety of cellular processes

2020

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“…The extent to which the regulation of PCD might still be relevant to eTudor and piRNA function, despite the loss of the DCD domain, remains to be elucidated, but there is evidence suggesting that it could be considerable. In the light of the putative evolutionary connection between the ancient form of PCD and the evolution of the eTudors and the piRNA network, it seems more explicable that conserved piRNA biogenesis factors Tudor-KH and MitoPLD/Zucchini are mitochondrially localized, perinuclear piRNA processing germ granules are also closely associated with mitochondria in addition to nuclear pores, and that reported phenotypes of many piRNA factor mutants include induction of PCD and/or germline mortality (Bronkhorst and Ketting 2018;Weick and Miska 2014;Houwing et al 2007;Tóth et al 2016;Aravin and Chan 2011;Manage et al 2020). PCD is an important part of tissue differentiation, and piRNAs can prevent ectopic expression of somatic genes that might contribute to PCD or senescence of the germline (Strome and Updike 2015;Meier, Finch, and Evan 2000).…”

Section: Discussionmentioning

confidence: 99%

Modified base-binding EVE and DCD Domains Implicated in the Origins of Programmed Cell Death and the piRNA Pathway

Bell

Wolf

Koonin

2020

Preprint

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BackgroundDNA and RNA of most cellular life forms and many viruses contain an expansive repertoire of modified bases. The modified bases play diverse biological roles that include both regulation of transcription and translation, and protection against restriction endonucleases and antibiotics. Modified bases are often recognized by dedicated protein domains. However, the elaborate networks of interactions and processes mediated by modified bases are far from being completely understood.ResultsWe present a comprehensive census and classification of EVE domains that belong to the PUA/ASCH domain superfamily and bind various modified bases in DNA and RNA. Prokaryotes encode two classes of EVE domain proteins, slow-evolving and fast-evolving. The slow-evolving EVE domains in α-proteobacteria are embedded in a conserved operonic context that implies involvement in coupling between translation and respiration, in particular, cytochrome c biogenesis, potentially, via binding 5-methylcytosine in tRNAs. In β and γ-proteobacteria, the conserved associations implicate the EVE domains in the coordination of cell division, biofilm formation, and global transcriptional regulation by non-coding 6S small RNAs, which are potentially modified and bound by the EVE domains. Down-regulation of the EVE-encoding operons might cause dormancy or programmed cell death (PCD). In eukaryotes, the EVE-domain-containing THYN1-like proteins appear to inhibit PCD and regulate the cell cycle, likely, via binding 5-methylcytosine and its derivatives in DNA and/or RNA. Thus, the link between PCD and cytochrome c that appears to be universal in eukaryotes might have been inherited from the α-proteobacterial, proto-mitochondrial endosymbiont and, unexpectedly, could involve modified base recognition by EVE domains. In numerous prokaryotic genomes, fast-evolving EVE domains are embedded in defense contexts, including toxin-antitoxin modules and Type IV restriction systems, all of which can also induce PCD. These EVE domains likely recognize modified bases in invading DNA molecules and target them for restriction. We additionally identified EVE-like prokaryotic Development and Cell Death (DCD) domains that are also implicated in defense functions including PCD. This function was inherited by eukaryotes but, in animals, the DCD proteins apparently were displaced by the extended Tudor family, whose partnership with Piwi-related Argonautes became the centerpiece of the piRNA system.ConclusionsRecognition of modified bases in DNA and RNA by EVE-like domains appears to be an important, but until now, under-appreciated, common denominator in a variety of processes including PCD, cell cycle control, antivirus immunity, stress response and germline development in animals.

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“…Associated with MIWI and MIWI2 via the binding of symmetrically dimethylated arginine (sDMA), TDRKH is the scaffold for interactions between PIWI-piRNA complexes and PNLDC1. The exonuclease trims the 3 -end of piRNA intermediates to their mature length (Ding et al, 2017;Zhang et al, 2017b;Bronkhorst and Ketting, 2018;Nishimura et al, 2018). The 3 -end of mature piRNA is 2 -O-methylated by HENMT1, yet correct 3 truncation is not necessary for 3 -end 2 -O-methylation (Yang et al, 2006;Zhai and Meyers, 2012;Peng et al, 2018).…”

Section: Primary Pirna Biogenesismentioning

confidence: 99%

“…Notably, LINE1 de-repression in spermatocytes does not necessarily lead to meiotic arrest, such as in Henmt1-knockout animals (Lim et al, 2015). Some mouse mutants of Miwi (Deng and Lin, 2002), Pnldc1 (Ding et al, 2017;Zhang et al, 2017c;Bronkhorst and Ketting, 2018;Nishimura et al, 2018), Tdrd5 (Yabuta et al, 2011;Ding et al, 2018), and Henmt1 (Lim et al, 2015), etc., still produce post-meiotic germ cells. Interestingly, although a large proportion of MIWI-piRNAs were thought to originate from non-transposon-related regions (Vourekas et al, 2012), LINE1 de-repression was found in Miwi-knockout mouse spermatids (Reuter et al, 2011).…”

Section: Repression Of Line1 Retrotransposons In Germ Cellsmentioning

confidence: 99%

Knockout Gene-Based Evidence for PIWI-Interacting RNA Pathway in Mammals

Zhang

Liu

2021

Front. Cell Dev. Biol.

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The PIWI-interacting RNA (piRNA) pathway mainly consists of evolutionarily conserved protein factors. Intriguingly, many mutations of piRNA pathway factors lead to meiotic arrest during spermatogenesis. The majority of piRNA factor-knockout animals show arrested meiosis in spermatogenesis, and only a few show post-meiosis male germ cell arrest. It is still unclear whether the majority of piRNA factors expressed in spermatids are involved in long interspersed nuclear element-1 repression after meiosis, but future conditional knockout research is expected to resolve this. In addition, recent hamster knockout studies showed that a piRNA factor is necessary for oocytes—in complete contrast to the findings in mice. This species discrepancy allows researchers to reexamine the function of piRNA in female germ cells. This mini-review focuses on the current knowledge of protein factors derived from mammalian knockout studies and summarizes their roles in the biogenesis and function of piRNAs.

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

Cited by 10 publications

References 12 publications

Modified base-binding EVE and DCD domains: striking diversity of genomic contexts in prokaryotes and predicted involvement in a variety of cellular processes

Modified base-binding EVE and DCD domains: striking diversity of genomic contexts in prokaryotes and predicted involvement in a variety of cellular processes

Modified base-binding EVE and DCD Domains Implicated in the Origins of Programmed Cell Death and the piRNA Pathway

Knockout Gene-Based Evidence for PIWI-Interacting RNA Pathway in Mammals

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