PIWI蛋白相互作用RNA与生殖功能的关系

doi:10.12280/gjszjk.20220479

摘要/Abstract

摘要：

PIWI蛋白相互作用RNA（PIWI-interacting RNA，piRNA）是长度大约有24~31个核苷酸的非编码RNA，特异性表达于动物的生殖细胞中。piRNA的生成过程可分为细胞核内的转录以及细胞质内的后期加工两部分。piRNA可以在PIWI家族蛋白的协助下发挥沉默转座子基因和调控mRNA等功能，并可进一步调控生殖功能。在雄性生殖功能中，piRNA可以在PIWI家族蛋白的协助下通过控制组蛋白泛素连接酶RNF8、谷胱甘肽过氧化物酶5等蛋白的表达调控精子发生，引起无精子症、少精子症和弱精子症等影响雄性生殖功能的疾病。在piRNA最初的研究中，学者普遍认为piRNA在雌性生殖方面作用不大，但是近年对金黄地鼠的研究发现piRNA/PIWI复合物在雌性生殖功能的调控过程中也发挥着重要作用。综述piRNA的产生及其与生殖功能的相关性。

关键词: RNA，非翻译, RNA，小分子干扰, 生殖, 卵母细胞, 不育，男（雄）性

Abstract:

PIWI-interacting RNA (piRNA), a kind of non-coding RNAs with a length of about 24-31 nucleotides, is specifically expressed in animal germ cells. The production process of piRNA can be divided into two parts: transcription in the nucleus and post-processing in the cytoplasm. piRNA can silence transcriptional genes, and regulates mRNA with the help of PIWI family proteins, and further regulates reproductive function. In male reproductive function, piRNA can control spermatogenesis by RNF8, glutathione peroxidase 5 and other proteins with the help of PIWI family proteins, resulting in azoospermia, oligozoospermia, asthenospermia and other diseases affecting male reproductive function. In the initial study of piRNA, researcher generally believed that piRNA had little effect on female reproduction. However, recent studies on golden hamsters found that piRNA/PIWI also played an important role in the regulation of female reproductive function. The production of piRNA and its correlation with reproductive function were reviewed.

Key words: RNA, untranslated, RNA, small interfering, Reproduction, Oocytes, Infertility, male

田辉, 张宇, 赵晓曦. PIWI蛋白相互作用RNA与生殖功能的关系[J]. 国际生殖健康/计划生育杂志, 2023, 42(2): 150-155.

TIAN Hui, ZHANG Yu, ZHAO Xiao-xi. The Relationship between PIWI-Interacting RNA and Reproductive Function[J]. Journal of International Reproductive Health/Family Planning, 2023, 42(2): 150-155.

参考文献 33

[1]	Liu Y, Dou M, Song X, et al. The emerging role of the piRNA/piwi complex in cancer[J]. Mol Cancer, 2019, 18(1):123. doi: 10.1186/s12943-019-1052-9. doi: 10.1186/s12943-019-1052-9 pmid: 31399034
[2]	Wang K, Wang T, Gao XQ, et al. Emerging functions of piwi-interacting RNAs in diseases[J]. J Cell Mol Med, 2021, 25(11):4893-4901. doi: 10.1111/jcmm.16466. doi: 10.1111/jcmm.16466 pmid: 33942984
[3]	Huang X, Fejes Tóth K, Aravin AA. piRNA Biogenesis in Drosophila melanogaster[J]. Trends Genet, 2017, 33(11):882-894. doi: 10.1016/j.tig.2017.09.002. doi: S0168-9525(17)30153-1 pmid: 28964526
[4]	Wu X, Pan Y, Fang Y, et al. The Biogenesis and Functions of piRNAs in Human Diseases[J]. Mol Ther Nucleic Acids, 2020, 21:108-120. doi: 10.1016/j.omtn.2020.05.023. doi: 10.1016/j.omtn.2020.05.023 URL
[5]	Sokolova OA, Ilyin AA, Poltavets AS, et al. Yb body assembly on the flamenco piRNA precursor transcripts reduces genic piRNA production[J]. Mol Biol Cell, 2019, 30(12):1544-1554. doi: 10.1091/mbc.E17-10-0591. doi: 10.1091/mbc.E17-10-0591 pmid: 30943101
[6]	Czech B, Munafò M, Ciabrelli F, et al. piRNA-Guided Genome Defense: From Biogenesis to Silencing[J]. Annu Rev Genet, 2018, 52:131-157. doi: 10.1146/annurev-genet-120417-031441. doi: 10.1146/annurev-genet-120417-031441 pmid: 30476449
[7]	Chen S, Ben S, Xin J, et al. The biogenesis and biological function of PIWI-interacting RNA in cancer[J]. J Hematol Oncol, 2021, 14(1):93. doi: 10.1186/s13045-021-01104-3. doi: 10.1186/s13045-021-01104-3
[8]	Sato K, Siomi MC. The piRNA pathway in Drosophila ovarian germ and somatic cells[J]. Proc Jpn Acad Ser B Phys Biol Sci, 2020, 96(1):32-42. doi: 10.2183/pjab.96.003. doi: 10.2183/pjab.96.003 URL
[9]	Ding X, Li Y, Lü J, et al. piRNA-823 Is Involved in Cancer Stem Cell Regulation Through Altering DNA Methylation in Association With Luminal Breast Cancer[J]. Front Cell Dev Biol, 2021, 9:641052. doi: 10.3389/fcell.2021.641052. doi: 10.3389/fcell.2021.641052 URL
[10]	Zoch A, Auchynnikava T, Berrens RV, et al. SPOCD1 is an essential executor of piRNA-directed de novo DNA methylation[J]. Nature, 2020, 584(7822):635-639. doi: 10.1038/s41586-020-2557-5. doi: 10.1038/s41586-020-2557-5
[11]	Schoeberl UE, Mochizuki K. Keeping the soma free of transposons: programmed DNA elimination in ciliates[J]. J Biol Chem, 2011, 286(43):37045-37052. doi: 10.1074/jbc.R111.276964. doi: 10.1074/jbc.R111.276964 pmid: 21914793
[12]	Mochizuki K. Developmentally programmed, RNA-directed genome rearrangement in Tetrahymena[J]. Dev Growth Differ, 2012, 54(1):108-119. doi: 10.1111/j.1440-169X.2011.01305.x. doi: 10.1111/j.1440-169X.2011.01305.x URL
[13]	Sun YH, Wang RH, Du K, et al. Coupled protein synthesis and ribosome-guided piRNA processing on mRNAs[J]. Nat Commun, 2021, 12(1):5970. doi: 10.1038/s41467-021-26233-8. doi: 10.1038/s41467-021-26233-8 pmid: 34645830
[14]	Watanabe T, Cheng EC, Zhong M, et al. Retrotransposons and pseudogenes regulate mRNAs and lncRNAs via the piRNA pathway in the germline[J]. Genome Res, 2015, 25(3):368-380. doi: 10.1101/gr.180802.114. doi: 10.1101/gr.180802.114 pmid: 25480952
[15]	Gou LT, Dai P, Yang JH, et al. Pachytene piRNAs instruct massive mRNA elimination during late spermiogenesis[J]. Cell Res, 2014, 24(6):680-700. doi: 10.1038/cr.2014.41. doi: 10.1038/cr.2014.41
[16]	Wang C, Yang ZZ, Guo FH, et al. Heat shock protein DNAJA1 stabilizes PIWI proteins to support regeneration and homeostasis of planarian Schmidtea mediterranea[J]. J Biol Chem, 2019, 294(25):9873-9887. doi: 10.1074/jbc.RA118.004445. doi: 10.1074/jbc.RA118.004445 pmid: 31076507
[17]	Ma C, Zhang L, Wang X, et al. piRNA-63076 contributes to pulmonary arterial smooth muscle cell proliferation through acyl-CoA dehydrogenase[J]. J Cell Mol Med, 2020, 24(9):5260-5273. doi: 10.1111/jcmm.15179. doi: 10.1111/jcmm.15179 pmid: 32227582
[18]	Han B, Jung BK, Park SH, et al. Polyubiquitin gene Ubb is required for upregulation of Piwi protein level during mouse testis development[J]. Cell Death Discov, 2021, 7(1):194. doi: 10.1038/s41420-021-00581-2. doi: 10.1038/s41420-021-00581-2 pmid: 34312369
[19]	Gou LT, Kang JY, Dai P, et al. Ubiquitination-Deficient Mutations in Human Piwi Cause Male Infertility by Impairing Histone-to-Protamine Exchange during Spermiogenesis[J]. Cell, 2017, 169(6):1090-1104.e13. doi: 10.1016/j.cell.2017.04.034. doi: 10.1016/j.cell.2017.04.034 URL
[20]	Dai P, Wang X, Gou LT, et al. A Translation-Activating Function of MIWI/piRNA during Mouse Spermiogenesis[J]. Cell, 2019, 179(7):1566-1581.e16. doi: 10.1016/j.cell.2019.11.022. doi: S0092-8674(19)31278-4 pmid: 31835033
[21]	Cornes E, Bourdon L, Singh M, et al. piRNAs initiate transcriptional silencing of spermatogenic genes during C. elegans germline development[J]. Dev Cell, 2022, 57(2):180-196.e7. doi: 10.1016/j.devcel.2021.11.025. doi: 10.1016/j.devcel.2021.11.025 URL
[22]	Xu L, Qiu L, Chang G, et al. Discovery of piRNAs Pathway Associated with Early-Stage Spermatogenesis in Chicken[J]. PLoS One, 2016, 11(4):e0151780. doi: 10.1371/journal.pone.0151780. doi: 10.1371/journal.pone.0151780 URL
[23]	Chu C, Yu L, Henry-Berger J, et al. Knockout of glutathione peroxidase 5 down-regulates the piRNAs in the caput epididymidis of aged mice[J]. Asian J Androl, 2020, 22(6):590-601. doi: 10.4103/aja.aja_3_20. doi: 10.4103/aja.aja_3_20 URL
[24]	Hutcheon K, McLaughlin EA, Stanger SJ, et al. Analysis of the small non-protein-coding RNA profile of mouse spermatozoa reveals specific enrichment of piRNAs within mature spermatozoa[J]. RNA Biol, 2017, 14(12):1776-1790. doi: 10.1080/15476286.2017.1356569. doi: 10.1080/15476286.2017.1356569 pmid: 28816603
[25]	Cao C, Wen Y, Wang X, et al. Testicular piRNA profile comparison between successful and unsuccessful micro-TESE retrieval in NOA patients[J]. J Assist Reprod Genet, 2018, 35(5):801-808. doi: 10.1007/s10815-018-1134-4. doi: 10.1007/s10815-018-1134-4
[26]	Nagirnaja L, Mørup N, Nielsen JE, et al. Variant PNLDC1, Defective piRNA Processing, and Azoospermia[J]. N Engl J Med, 2021, 385(8):707-719. doi: 10.1056/NEJMoa2028973. doi: 10.1056/NEJMoa2028973 URL
[27]	Choi H, Wang Z, Dean J. Sperm acrosome overgrowth and infertility in mice lacking chromosome 18 pachytene piRNA[J]. PLoS Genet, 2021, 17(4):e1009485. doi: 10.1371/journal.pgen.1009485. doi: 10.1371/journal.pgen.1009485 URL
[28]	Shen L, Yu C, Wu Y, et al. Transcriptomic landscape of GC-2spd(ts) cell in response to the downregulation of piR-1207/2107[J]. Andrologia, 2022, 54(9):e14522. doi: 10.1111/and.14522. doi: 10.1111/and.14522
[29]	Carmell MA, Girard A, van de Kant HJ, et al. MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline[J]. Dev Cell, 2007, 12(4):503-514. doi: 10.1016/j.devcel.2007.03.001. doi: 10.1016/j.devcel.2007.03.001 pmid: 17395546
[30]	Huang H, Gao Q, Peng X, et al. piRNA-associated germline nuage formation and spermatogenesis require MitoPLD profusogenic mitochondrial-surface lipid signaling[J]. Dev Cell, 2011, 20(3):376-387. doi: 10.1016/j.devcel.2011.01.004. doi: 10.1016/j.devcel.2011.01.004 pmid: 21397848
[31]	Zhang H, Zhang F, Chen Q, et al. The piRNA pathway is essential for generating functional oocytes in golden hamsters[J]. Nat Cell Biol, 2021, 23(9):1013-1022. doi: 10.1038/s41556-021-00750-6. doi: 10.1038/s41556-021-00750-6 pmid: 34489574
[32]	Li Y, Liang Z, Liang Z, et al. Abnormal PIWI-interacting RNA profile and its association with the deformed extracellular matrix of oocytes from recurrent oocyte maturation arrest patients[J]. Fertil Steril, 2021, 115(5):1318-1326. doi: 10.1016/j.fertnstert.2020.11.037. doi: 10.1016/j.fertnstert.2020.11.037 pmid: 33622565
[33]	Hutt KJ, Lim SL, Zhang QH, et al. HENMT1 is involved in the maintenance of normal female fertility in the mouse[J]. Mol Hum Reprod, 2021, 27(11):gaab061. doi: 10.1093/molehr/gaab061. doi: 10.1093/molehr/gaab061 URL