Pachytene PiRNAs Control Discrete Meiotic Events During Spermatogenesis and Restrict Gene Expression in Space and Time

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2024 Oct 2

PMID 39356768

Authors

Jacob Ortega

Lamia Wahba

Jacob Seemann

Shin-Yu Chen

Andrew Z Fire

Swathi Arur

Affiliations

Soon will be listed here.

Abstract

Pachytene piRNAs, a Piwi-interacting RNA subclass in mammals, are hypothesized to regulate non-transposon sequences during spermatogenesis. piRNAs, the 21URNAs, are implicated in regulating coding sequences; the messenger RNA targets and biological processes they control during spermatogenesis are largely unknown. We demonstrate that loss of 21URNAs compromises homolog pairing and makes it permissive for nonhomologous synapsis resulting in defects in crossover formation and chromosome segregation during spermatogenesis. We identify Polo-like kinase 3 (PLK-3), among others, as a 21URNA target. 21URNA activity restricts PLK-3 protein to proliferative cells, and expansion of PLK-3 in pachytene overlaps with the meiotic defects. Removal of results in quantitative genetic suppression of the meiotic defects. One discrete 21URNA inhibits PLK-3 expression in late pachytene cells. Together, these results suggest that the 21URNAs function as pachytene piRNAs during spermatogenesis. We identify their targets and meiotic events and highlight the remarkable intricacy of this multi-effector mechanism during spermatogenesis.

References

Woglar A, Daryabeigi A, Adamo A, Habacher C, Machacek T, La Volpe A . Matefin/SUN-1 phosphorylation is part of a surveillance mechanism to coordinate chromosome synapsis and recombination with meiotic progression and chromosome movement. PLoS Genet. 2013; 9(3):e1003335. PMC: 3591285. DOI: 10.1371/journal.pgen.1003335. View

Czech B, Munafo M, Ciabrelli F, Eastwood E, Fabry M, Kneuss E . piRNA-Guided Genome Defense: From Biogenesis to Silencing. Annu Rev Genet. 2018; 52:131-157. PMC: 10784713. DOI: 10.1146/annurev-genet-120417-031441. View

Bartel D . Metazoan MicroRNAs. Cell. 2018; 173(1):20-51. PMC: 6091663. DOI: 10.1016/j.cell.2018.03.006. View

Gervaise A, Arur S . Spatial and Temporal Analysis of Active ERK in the C. elegans Germline. J Vis Exp. 2016; (117). PMC: 5226324. DOI: 10.3791/54901. View

Kuramochi-Miyagawa S, Kimura T, Ijiri T, Isobe T, Asada N, Fujita Y . Mili, a mammalian member of piwi family gene, is essential for spermatogenesis. Development. 2004; 131(4):839-49. DOI: 10.1242/dev.00973. View

Avery L, Wasserman S . Ordering gene function: the interpretation of epistasis in regulatory hierarchies. Trends Genet. 1992; 8(9):312-6. PMC: 3955268. DOI: 10.1016/0168-9525(92)90263-4. View

Choi C, Tay R, Starostik M, Feng S, Moresco J, Montgomery B . SNPC-1.3 is a sex-specific transcription factor that drives male piRNA expression in . Elife. 2021; 10. PMC: 7884074. DOI: 10.7554/eLife.60681. View

Kim K, Tang N, Andrusiak M, Wu Z, Chisholm A, Jin Y . A Neuronal piRNA Pathway Inhibits Axon Regeneration in C. elegans. Neuron. 2018; 97(3):511-519.e6. PMC: 5866297. DOI: 10.1016/j.neuron.2018.01.014. View

Homolka D, Pandey R, Goriaux C, Brasset E, Vaury C, Sachidanandam R . PIWI Slicing and RNA Elements in Precursors Instruct Directional Primary piRNA Biogenesis. Cell Rep. 2015; 12(3):418-28. DOI: 10.1016/j.celrep.2015.06.030. View

10.

Aravin A, Sachidanandam R, Girard A, Fejes-Toth K, Hannon G . Developmentally regulated piRNA clusters implicate MILI in transposon control. Science. 2007; 316(5825):744-7. DOI: 10.1126/science.1142612. View

11.

Yokoo R, Zawadzki K, Nabeshima K, Drake M, Arur S, Villeneuve A . COSA-1 reveals robust homeostasis and separable licensing and reinforcement steps governing meiotic crossovers. Cell. 2012; 149(1):75-87. PMC: 3339199. DOI: 10.1016/j.cell.2012.01.052. View

12.

Gruidl M, Smith P, Kuznicki K, McCrone J, Kirchner J, Roussell D . Multiple potential germ-line helicases are components of the germ-line-specific P granules of Caenorhabditis elegans. Proc Natl Acad Sci U S A. 1996; 93(24):13837-42. PMC: 19442. DOI: 10.1073/pnas.93.24.13837. View

13.

Okamura K, Lai E . Endogenous small interfering RNAs in animals. Nat Rev Mol Cell Biol. 2008; 9(9):673-8. PMC: 2729316. DOI: 10.1038/nrm2479. View

14.

Zheng K, Wang P . Blockade of pachytene piRNA biogenesis reveals a novel requirement for maintaining post-meiotic germline genome integrity. PLoS Genet. 2012; 8(11):e1003038. PMC: 3499362. DOI: 10.1371/journal.pgen.1003038. View

15.

Maniar J, Fire A . EGO-1, a C. elegans RdRP, modulates gene expression via production of mRNA-templated short antisense RNAs. Curr Biol. 2011; 21(6):449-59. PMC: 3073447. DOI: 10.1016/j.cub.2011.02.019. View

16.

Seroussi U, Lugowski A, Wadi L, Lao R, Willis A, Zhao W . A comprehensive survey of argonaute proteins reveals organism-wide gene regulatory networks and functions. Elife. 2023; 12. PMC: 10101689. DOI: 10.7554/eLife.83853. View

17.

Woglar A, Villeneuve A . Dynamic Architecture of DNA Repair Complexes and the Synaptonemal Complex at Sites of Meiotic Recombination. Cell. 2018; 173(7):1678-1691.e16. PMC: 6003859. DOI: 10.1016/j.cell.2018.03.066. View

18.

De Fazio S, Bartonicek N, Di Giacomo M, Abreu-Goodger C, Sankar A, Funaya C . The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements. Nature. 2011; 480(7376):259-63. DOI: 10.1038/nature10547. View

19.

Ortiz M, Noble D, Sorokin E, Kimble J . A new dataset of spermatogenic vs. oogenic transcriptomes in the nematode Caenorhabditis elegans. G3 (Bethesda). 2014; 4(9):1765-72. PMC: 4169169. DOI: 10.1534/g3.114.012351. View

20.

Gao G, Deeb F, Mercurio J, Parfenova A, Smith P, Bennett K . PAN-1, a P-granule component important for C. elegans fertility, has dual roles in the germline and soma. Dev Biol. 2012; 364(2):202-13. DOI: 10.1016/j.ydbio.2012.02.006. View