Sperm-borne Small Non-coding RNAs: Potential Functions and Mechanisms As Epigenetic Carriers

Overview

Journal Cell Biosci

Publisher Biomed Central

Date 2025 Jan 17

PMID 39825433

Authors

Muhammad Naveed

Zhaokang Shen

Jianqiang Bao

Affiliations

Soon will be listed here.

Abstract

Over the past two decades, the study of sperm-borne small non-coding RNAs (sncRNAs) has garnered substantial growth. Once considered mere byproducts during germ cell maturation, these sncRNAs have now been recognized as crucial carriers of epigenetic information, playing a significant role in transmitting acquired traits from paternal to offspring, particularly under environmental influences. A growing body of evidence highlights the pivotal role of these sncRNAs in facilitating epigenetic inheritance across generations. However, the exact mechanisms through which these paternally supplied epigenetic carriers operate remain unclear and are under hot debate. This concise review presents the most extensive evidence to date on environmentally-responsive sperm-borne sncRNAs, encompassing brief summary of their origin, dynamics, compartmentalization, characteristics, as well as in-depth elaboration of their functional roles in epigenetic and transgenerational inheritance. Additionally, the review delves into the potential mechanisms by which sperm-delivered sncRNAs may acquire and transmit paternally acquired traits to offspring, modulating zygotic gene expression and influencing early embryonic development.

References

Salas-Huetos A, Blanco J, Vidal F, Grossmann M, Pons M, Garrido N . Spermatozoa from normozoospermic fertile and infertile individuals convey a distinct miRNA cargo. Andrology. 2016; 4(6):1028-1036. DOI: 10.1111/andr.12276. View

Chan J, Morgan C, Leu N, Shetty A, Cisse Y, Nugent B . Reproductive tract extracellular vesicles are sufficient to transmit intergenerational stress and program neurodevelopment. Nat Commun. 2020; 11(1):1499. PMC: 7083921. DOI: 10.1038/s41467-020-15305-w. View

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

Peng H, Shi J, Zhang Y, Zhang H, Liao S, Li W . A novel class of tRNA-derived small RNAs extremely enriched in mature mouse sperm. Cell Res. 2012; 22(11):1609-12. PMC: 3494397. DOI: 10.1038/cr.2012.141. View

Fu H, Feng J, Liu Q, Sun F, Tie Y, Zhu J . Stress induces tRNA cleavage by angiogenin in mammalian cells. FEBS Lett. 2008; 583(2):437-42. DOI: 10.1016/j.febslet.2008.12.043. View

Djuranovic S, Nahvi A, Green R . miRNA-mediated gene silencing by translational repression followed by mRNA deadenylation and decay. Science. 2012; 336(6078):237-40. PMC: 3971879. DOI: 10.1126/science.1215691. View

Wang Y, Chen Z, Hu H, Lei J, Zhou Z, Yao B . Sperm microRNAs confer depression susceptibility to offspring. Sci Adv. 2021; 7(7). PMC: 7875527. DOI: 10.1126/sciadv.abd7605. View

Miller D, Briggs D, Snowden H, Hamlington J, Rollinson S, Lilford R . A complex population of RNAs exists in human ejaculate spermatozoa: implications for understanding molecular aspects of spermiogenesis. Gene. 1999; 237(2):385-92. DOI: 10.1016/s0378-1119(99)00324-8. View

Lim L, Lau N, Garrett-Engele P, Grimson A, Schelter J, Castle J . Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005; 433(7027):769-73. DOI: 10.1038/nature03315. View

10.

Nixon B, Stanger S, Mihalas B, Reilly J, Anderson A, Tyagi S . The microRNA signature of mouse spermatozoa is substantially modified during epididymal maturation. Biol Reprod. 2015; 93(4):91. DOI: 10.1095/biolreprod.115.132209. View

11.

Amanai M, Brahmajosyula M, Perry A . A restricted role for sperm-borne microRNAs in mammalian fertilization. Biol Reprod. 2006; 75(6):877-84. DOI: 10.1095/biolreprod.106.056499. View

12.

Li K, Zhou T, Liao L, Yang Z, Wong C, Henn F . βCaMKII in lateral habenula mediates core symptoms of depression. Science. 2013; 341(6149):1016-20. PMC: 3932364. DOI: 10.1126/science.1240729. View

13.

Ridder K, Keller S, Dams M, Rupp A, Schlaudraff J, Del Turco D . Extracellular vesicle-mediated transfer of genetic information between the hematopoietic system and the brain in response to inflammation. PLoS Biol. 2014; 12(6):e1001874. PMC: 4043485. DOI: 10.1371/journal.pbio.1001874. View

14.

Smorag L, Zheng Y, Nolte J, Zechner U, Engel W, Pantakani D . MicroRNA signature in various cell types of mouse spermatogenesis: evidence for stage-specifically expressed miRNA-221, -203 and -34b-5p mediated spermatogenesis regulation. Biol Cell. 2012; 104(11):677-92. DOI: 10.1111/boc.201200014. View

15.

Sarker G, Sun W, Rosenkranz D, Pelczar P, Opitz L, Efthymiou V . Maternal overnutrition programs hedonic and metabolic phenotypes across generations through sperm tsRNAs. Proc Natl Acad Sci U S A. 2019; 116(21):10547-10556. PMC: 6534971. DOI: 10.1073/pnas.1820810116. View

16.

Boccaletto P, Stefaniak F, Ray A, Cappannini A, Mukherjee S, Purta E . MODOMICS: a database of RNA modification pathways. 2021 update. Nucleic Acids Res. 2021; 50(D1):D231-D235. PMC: 8728126. DOI: 10.1093/nar/gkab1083. View

17.

Zheng G, Qin Y, Clark W, Dai Q, Yi C, He C . Efficient and quantitative high-throughput tRNA sequencing. Nat Methods. 2015; 12(9):835-837. PMC: 4624326. DOI: 10.1038/nmeth.3478. View

18.

Gan M, Jing Y, Xie Z, Ma J, Chen L, Zhang S . Potential Function of Testicular MicroRNAs in Heat-Stress-Induced Spermatogenesis Disorders. Int J Mol Sci. 2023; 24(10). PMC: 10218599. DOI: 10.3390/ijms24108809. View

19.

Cozen A, Quartley E, Holmes A, Hrabeta-Robinson E, Phizicky E, Lowe T . ARM-seq: AlkB-facilitated RNA methylation sequencing reveals a complex landscape of modified tRNA fragments. Nat Methods. 2015; 12(9):879-84. PMC: 4553111. DOI: 10.1038/nmeth.3508. View

20.

Jodar M, Selvaraju S, Sendler E, Diamond M, Krawetz S . The presence, role and clinical use of spermatozoal RNAs. Hum Reprod Update. 2013; 19(6):604-24. PMC: 3796946. DOI: 10.1093/humupd/dmt031. View