The DOI matches its Crossref record; 42 of the 50 references it cites were found in a registry or an index.
Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs
Open accessAbstract
The discovery of RNAs (for example, messenger RNAs, non-coding RNAs) in sperm has opened the possibility that sperm may function by delivering additional paternal information aside from solely providing the DNA 1 . Increasing evidence now suggests that sperm small non-coding RNAs (sncRNAs) can mediate intergenerational transmission of paternally acquired phenotypes, including mental stress 2,3 and metabolic disorders 4-6. How sperm sncRNAs encode paternal information remains unclear, but the mechanism may involve RNA modifications. Here we show that deletion of a mouse tRNA methyltransferase, DNMT2, abolished sperm sncRNA-mediated transmission of high-fat-diet-induced metabolic disorders to offspring. Dnmt2 deletion prevented the elevation of RNA modifications (m 5 C, m 2 G) in sperm 30-40 nt RNA fractions that are induced by a high-fat diet. Also, Dnmt2 deletion altered the sperm small RNA expression profile, including levels of tRNA-derived small RNAs and rRNA-derived small RNAs, which might be essential in composing a sperm RNA 'coding signature' that is needed for paternal epigenetic memory. Finally, we show that Dnmt2-mediated m 5 C contributes to the secondary structure and biological properties of sncRNAs, implicating sperm RNA modifications as an additional layer of paternal hereditary information.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“it has since been discovered that sperm‐derived mtRNA can respond to environmental cues and affect subsequent offspring development and health trajectories [34, 35, 36, 37].”
From Ignoring the planet: A critical blind spot for research on ageing (2025) · cites this paper as [36]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849
Near-optimal probabilistic RNA-seq quantification
Bray, N. L., Pimentel, H., Melsted, P., & Pachter, L. (2016) · Nature Biotechnology · doi:10.1038/nbt.3519 · Cited by 9,723 · cited 1×
“RNA Annotation— RNA sequences were annotated using kallisto 39 with Ensembl mouse cDNA annotation information (GRCm38).”
The DNA methyltransferase family: a versatile toolkit for epigenetic regulation
Lyko, F. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.80 · Cited by 1,510 · cited 2×
“These mechanisms could be highly relevant to human health because the structure and function of DNMT2 are highly conserved, and have been harnessed to respond to environmental challenges during evolution 15, 36 .”
Self-citationSperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder
Chen, Q., Yan, M., Cao, Z., Li, X., Zhang, Y., Shi, J., Feng, G.-H., Peng, H., Zhang, X., Zhang, Y., et al. (2016) · Science · doi:10.1126/science.aad7977 · Cited by 1,470 · cited 9×
“Increasing evidence now suggests that sperm small non-coding RNAs (sncRNAs) can mediate intergenerational transmission of paternally acquired phenotypes, including mental stress 2, 3 and metabolic disorders 4–6 .”
InfluentialSelf-citationImplication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice
Gapp, K., Jawaid, A., Sarkies, P., Bohacek, J., Pelczar, P., Prados, J., Farinelli, L., Miska, E., & Mansuy, I. M. (2014) · Nature Neuroscience · doi:10.1038/nn.3695 · Cited by 1,306 · cited 3×
“Increasing evidence now suggests that sperm small non-coding RNAs (sncRNAs) can mediate intergenerational transmission of paternally acquired phenotypes, including mental stress 2, 3 and metabolic disorders 4–6 .”
Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals
Sharma, U., Conine, C. C., Shea, J. M., Boskovic, A., Derr, A. G., Bing, X. Y., Belleannee, C., Kucukural, A., Serra, R. W., Sun, F., et al. (2016) · Science · doi:10.1126/science.aad6780 · Cited by 1,275 · cited 4×
“1b) (a segment of male reproductive tract where sperm undergo maturation, and fine-tuning of sperm tsRNA composition 6 ).”
InfluentialMethylation of tRNA Asp by the DNA Methyltransferase Homolog Dnmt2
Goll, M. G., Kirpekar, F., Maggert, K. A., Yoder, J. A., Hsieh, C., Zhang, X., Golic, K. G., Jacobsen, S. E., & Bestor, T. H. (2006) · Science · doi:10.1126/science.1120976 · Cited by 1,192 · cited 2×
“This is consistent with previous reports that DNMT2 does not affect RNA modifications in large RNAs 16 .”
Self-citationTransgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress
Rodgers, A. B., Morgan, C. P., Leu, N. A., & Bale, T. L. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1508347112 · Cited by 751 · cited 2×
“Increasing evidence now suggests that sperm small non-coding RNAs (sncRNAs) can mediate intergenerational transmission of paternally acquired phenotypes, including mental stress 2, 3 and metabolic disorders 4–6 .”
RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis
Tuorto, F., Liebers, R., Musch, T., Schaefer, M., Hofmann, S., Kellner, S. M., Frye, M., Helm, M., Stoecklin, G., & Lyko, F. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2357 · Cited by 635 · cited 4×
“The loss of m 5 C at C38 can facilitate tRNA fragmentation, which leads to excessive amounts of tsRNAs and may elicit pathophysiological conditions 17, 18 .”
InfluentialSelf-citationIn utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism
Radford, E. J., Ito, M., Shi, H., Corish, J. A., Yamazawa, K., ISGANAITIS, E. M., Seisenberger, S., Hore, T. A., Reik, W., Erkek, S., et al. (2014) · Science · doi:10.1126/science.1255903 · Cited by 627
Cited by
Sorted by citations
Items 101–200 of 400
Molecular insights into the transgenerational inheritance of stress memory
Zhang, Q., & Tian, Y. (2021) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2021.11.015 · Cited by 51
Engineering exosomes for bone defect repair
Ma, S., Zhang, Y., Li, S., Li, A., Li, Y., & Pei, D. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.1091360 · Cited by 38
Self-citationEpididymal acquired sperm microRNAs modify post-fertilization embryonic gene expression
Trigg, N. A., & Conine, C. C. (2023) · bioRxiv · doi:10.1101/2023.10.01.560377 · Cited by 37
“…identified environmentally induced alterations in the epididymal soma that could conceivably contribute to the delivery of an altered small RNA payload to sperm, including modulation to transcription factors and RNA methyltransferases (Rompala et al., 2018; Trigg et al., 2021; Zhang et al., 2018).”
BackgroundThe epitranscriptome of small non-coding RNAs
Li, X., Peng, J., & Yi, C. (2021) · Non-coding RNA Research · doi:10.1016/j.ncrna.2021.10.002 · Cited by 47
Self-citationNovel insights into the roles of tRNA-derived small RNAs
Pan, Q., Han, T., & Li, G. (2021) · RNA Biology · doi:10.1080/15476286.2021.1922009 · Cited by 45
Raad, G., Serra, F., Martin, L., Derieppe, M., Gilleron, J., Costa, V. L., Pisani, D. F., Amri, E., Trabucchi, M., & Grandjean, V. (2021) · eLife · doi:10.7554/elife.61736 · Cited by 50
Ribas‐Maynou, J., Yeste, M., & Salas‐Huetos, A. (2020) · Biology · doi:10.3390/biology9070178 · Cited by 49
“Regarding the sperm epigenome, it has been demonstrated that oxidative stress induces tRNA cleavage [71], generating tsRNA and rRNA fragments that are involved in the sperm-mediated inheritance of intergenerational pathologies [68,72].”
BackgroundSperm RNA Payload: Implications for Intergenerational Epigenetic Inheritance
Liu, S., & Sharma, U. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065889 · Cited by 41
“Sperm of HFD mice showed an overall increase in the levels of tRFs. Intriguingly, embryos injected with 30–40 nts RNAs (corresponding to tRF size) purified from high-fat sperm produced offspring with altered glucose tolerance, suggesting that tRFs (and other sperm RNAs of 30–40 nts size range) are responsible for the…”
BackgroundInfluentialSelf-citationRisal, S., Li, C., Luo, Q., Fornes, R., Lu, H., Eriksson, G., Manti, M., Ohlsson, C., Lindgren, E., Crisosto, N., et al. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101035 · Cited by 47
Mechanisms of transgenerational epigenetic inheritance: lessons from animal model organisms
Santilli, F., & Bošković, A. (2023) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2023.102024 · Cited by 34
Wang, B., Lin, X., Zhu, D., Zeng, H., Wei, B. K., Lu, L., Li, W., Shi, Y., Liu, J., Zhang, Y., et al. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.857875 · Cited by 33
Self-citationEpigenetic Mechanisms of Paternal Stress in Offspring Development and Diseases
Xu, X., Miao, Z., Sun, M., & Wan, B. (2021) · International Journal of Genomics · doi:10.1155/2021/6632719 · Cited by 39
“DNA methylation, histone modification, and sncRNAs interact with each other [73, 101].”
BackgroundPaternal Nongenetic Intergenerational Transmission of Metabolic Disease Risk
Su, L., & Patti, M. (2019) · Current Diabetes Reports · doi:10.1007/s11892-019-1163-0 · Cited by 35
Hernandez, R., Shi, J., Liu, J., Li, X., Wu, J., Zhao, L., Zhou, T., Chen, Q., & Zhou, C. (2023) · Journal of Lipid Research · doi:10.1016/j.jlr.2023.100352 · Cited by 36
Self-citationSmall Noncoding RNAs in Reproduction and Infertility
Zhu, Q., Kirby, J. A., Chu, C., & Gou, L. (2021) · Biomedicines · doi:10.3390/biomedicines9121884 · Cited by 41
“Given that RNA modifications are rich in tRNAs and rRNAs and contribute to the generation of tsRNAs and rsRNAs [84,85], the resulting tsRNAs and rsRNAs are likely to inherit those modifications.”
BackgroundInfluentialNon-genetic inheritance via the male germline in mammals
Baxter, F., & Drake, A. J. (2019) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2018.0118 · Cited by 41
Fazio, A. D., & Gullerová, M. (2023) · British Journal of Cancer · doi:10.1038/s41416-023-02191-4 · Cited by 35
“Ablation of DNMT2 in mouse sperm has been associated with the increase of a set of tsRNAs [71, 72].”
Background150 years of Darwin’s theory of intercellular flow of hereditary information
Liu, Y.-S., & Chen, Q. (2018) · Nature reviews. Molecular cell biology · doi:10.1038/s41580-018-0072-4 · Cited by 32
Self-citationMorgan, C. P., Shetty, A. C., Chan, J. C., Berger, D. S., Ament, S. A., Epperson, C. N., & Bale, T. L. (2020) · Scientific Reports · doi:10.1038/s41598-020-73867-7 · Cited by 33
Zhang, J., Xiong, Y.-W., Tan, L., Zheng, X., Zhang, Y., Ling, Q., Zhang, C., Zhu, H.-L., Chang, W., & Wang, H. (2023) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2023.131891 · Cited by 32
Self-citationJimenez, N. A., Castellano, M., Santillán, E. M., Boulias, K., Boan, A. F., Padilla, L. F. A., Fernandino, J. I., Greer, E. L., Tosar, J. P., Cochella, L., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37427-7 · Cited by 34
Role of small RNAs harbored by sperm in embryonic development and offspring phenotype
Chen, Y., Zeng, Q., Liu, J., Yeung, W. S. B., Zhang, J. V., & Duan, Y. (2022) · Andrology · doi:10.1111/andr.13347 · Cited by 37
Dietary Micronutrient Supplementation for 12 Days in Obese Male Mice Restores Sperm Oxidative Stress
McPherson, N. O., Shehadeh, H., Fullston, T., Zander‐Fox, D., & Lane, M. (2019) · Nutrients · doi:10.3390/nu11092196 · Cited by 32
The tRNA-associated dysregulation in diabetes mellitus
Zhou, Z. G., Sun, B., Huang, S., Jia, W., & Yu, D. (2019) · Metabolism · doi:10.1016/j.metabol.2019.01.017 · Cited by 31
Wu, Z., Zhou, R., Li, B., Cao, M., Wang, W., & Li, X. (2024) · Cell Proliferation · doi:10.1111/cpr.13692 · Cited by 27
“127 These findings shed light on the intricate regulatory mechanisms governing tRNA modifications and their impact on protein synthesis and epigenetic processes.”
BackgroundSelf-citationWei, X., Zhang, Z., Gu, Y., Zhang, R., Huang, J., Li, F., He, Y., Lu, S., Wu, Y., Zeng, W., et al. (2024) · Cell Discovery · doi:10.1038/s41421-024-00657-0 · Cited by 31
Self-citationHypoxia induces alterations in tRNA modifications involved in translational control
Guo, H., Lin, X., Wang, W., Xu, W., Shen, X., Wu, X., He, T., Jiang, X., Xu, Y., Zhao, P., et al. (2023) · BMC Biology · doi:10.1186/s12915-023-01537-x · Cited by 36
“After staining the gel by SYBR GOLD (Invitrogen, catalog number: S11494), ~80-nt and 17–50-nt RNA fragments were excised and recycled from the gel according to RNA Ladder (NEB, catalog number: N0364S and N2102S) as we previously reported [45].”
BackgroundMethodInfluentialSelf-citationEmerging functions of tRNA modifications in mRNA translation and diseases
Wang, L., & Lin, S. (2022) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2022.10.002 · Cited by 28
Modifications of the human tRNA anticodon loop and their associations with genetic diseases
Zhou, J.-B., Wang, E., & Zhou, X.-L. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03948-x · Cited by 37
Bohacek, J., & Rassoulzadegan, M. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.07.005 · Cited by 31
Lin, X., Guo, H., Wu, X., Xu, Y., Zhao, P., Yan, B., Zeng, Y., He, Y., Chen, D., Gale, R. P., et al. (2023) · Theranostics · doi:10.7150/thno.80054 · Cited by 35
“Northern blotting was performed as previously described [6] to verify the expression pattern of tsRNA (tsRNA-GlyCCC) and ysRNA (ysRNARNA4 and ysRNARNY5) in PBS of healthy controls.”
Self-citationLi, Z.-G., Qi, X.-L., Zhang, X., Yu, L., Gao, L., Kong, W.-L., Chen, W., Dong, W., Luo, L., Lu, D., et al. (2022) · Animal Models and Experimental Medicine · doi:10.1002/ame2.12221 · Cited by 28
Self-citationEpitranscriptomics: A New Layer of microRNA Regulation in Cancer
Paolis, V. D., Lorefice, E., Orecchini, E., Carissimi, C., Laudadio, I., & Fulci, V. (2021) · Cancers · doi:10.3390/cancers13133372 · Cited by 37
“…poorly understood so far; nevertheless, this modification has been recently highlighted in vault RNAs (vtRNAs) [158], piwi-associated RNAs (piRNAs) [169] and miRNAs [91,170,171]. m5C deposition regulates the processing of vault ncRNAs into small vault RNAs (svRNAs) [158,172]. m5C has been only…”
The occurrence order and cross-talk of different tRNA modifications
Li, J., Zhu, W., Yang, W., Li, C., & Liu, R. (2021) · Science China Life Sciences · doi:10.1007/s11427-020-1906-4 · Cited by 31
The Life of MicroRNAs: Biogenesis, Function and Decay in Cancer
Ding, S., & Wang, P. (2025) · Biomolecules · doi:10.3390/biom15101393 · Cited by 27
“Additionally, tsRNAs are generally heavily modified, a feature required for transgenerational inheritance [225], which may also differentially impact RISC function.”
Small RNA and Toll-like receptor interactions: origins and disease mechanisms
Yu, J., Zhang, X., Cai, C., Zhou, T., & Chen, Q. (2025) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2025.01.004 · Cited by 27
Self-citationCai, J., Li, C., Liu, S., Tan, M., Sun, Y., Sun, X., Yang, M., & He, B. (2024) · Cell Death and Differentiation · doi:10.1038/s41418-024-01311-8 · Cited by 31
Self-citationtRNA ‐derived RNAs : Biogenesis and roles in translational control
Akiyama, Y., & Ivanov, P. V. (2023) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1805 · Cited by 35
“Additionally in mice, Dnmt2-mediated RNA methylations (m 5 C and m 2 G) are required for tDR-containing sperm-mediated transmission of metabolic phenotypes to offspring (Y. Zhang et al., 2018).”
BackgroundLack of evidence for intergenerational inheritance of immune resistance to infections
Kaufmann, E., Landekic, M., Downey, J., Chronopoulos, J., Nezhad, S. T., Tran, K., Vinh, D., Barreiro, L. B., & Divangahi, M. (2022) · Nature Immunology · doi:10.1038/s41590-021-01102-0 · Cited by 27
MicroRNAs and tRNA-Derived Small Fragments: Key Messengers in Nuclear–Mitochondrial Communication
Meseguer, S. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.643575 · Cited by 28
Germ cell-mediated mechanisms of epigenetic inheritance
Lempradl, A. M. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.07.012 · Cited by 36
tRNA derived small RNAs—Small players with big roles
George, S., Rafi, M., Aldarmaki, M., ElSiddig, M., Nuaimi, M. A., & Amiri, K. M. A. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.997780 · Cited by 35
“Post-transcriptional modifications of tRFs are potentially important in intergenerational inheritance of metabolic disorders as deletion of tRNA methyltransferase, DNMT2, abolished sperm sncRNA-mediated transmission of high-fat diet-induced metabolic disorders to offspring (Zhang et al., 2018).”
BackgroundTransfer RNA-derived small RNAs (tsRNAs): Versatile regulators in cancer
Xu, D., Qiao, D., Lei, Y., Zhang, C., Bu, Y., & Zhang, Y. (2022) · Cancer Letters · doi:10.1016/j.canlet.2022.215842 · Cited by 33
Self-citationChemical biology and medicinal chemistry of RNA methyltransferases
Fischer, T. R., Meidner, J. L., Schwickert, M., Weber, M., Zimmermann, R. A., Kersten, C., Schirmeister, T., & Helm, M. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac224 · Cited by 37
“Further prospects for future drug development may be found in human MTases that affect viral replication (214–217), or epigenetic inheritance (218,219).”
BackgroundDeep sequencing of yeast and mouse tRNAs and tRNA fragments using OTTR
Gustafsson, H. T., Ferguson, L., Galan, C., Yu, T.-X., Upton, H. E., Kaymak, E., Weng, Z., Collins, K., & Rando, O. J. (2022) · bioRxiv · doi:10.1101/2022.02.04.479139 · Cited by 26
“Second, Northern blotting studies in sperm and epididymis samples revealed the presence of 3' tRNA halves that are not represented in deep sequencing datasets [16, 17], further emphasizing our incomplete understanding of the mammalian sperm RNA payload.”
BackgroundInfluentialGapp, K., Parada, G. E., Groß, F., Corcoba, A., Kaur, J., Grau, E., Hemberg, M., Bohacek, J., & Miska, E. A. (2021) · iScience · doi:10.1016/j.isci.2021.102870 · Cited by 34
Sun, W., von Meyenn, F., Peleg‐Raibstein, D., & Wolfrum, C. (2019) · Advanced Science · doi:10.1002/advs.201900275 · Cited by 31
5-Methylcytosine RNA modification and its roles in cancer and cancer chemotherapy resistance
Fang, L., Liu, T., Dong, Y., Gao, Q., Lu, R., & Deng, Z. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06217-8 · Cited by 23
“While DNMT2 was found to mediate m5C methylation modification of DNA, DNMT2 also mediates m5C modification of tRNA [25].”
Sperm-borne small non-coding RNAs: potential functions and mechanisms as epigenetic carriers
Naveed, M., Shen, Z., & Bao, J. (2025) · Cell & Bioscience · doi:10.1186/s13578-025-01347-4 · Cited by 30
“This disruption ultimately prevents the transmission of HFD-induced metabolic conditions from parent to progeny [126].”
A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription
Li, H., Han, D. H., Xu, B., Xiong, Q., Li, C., Yang, W., Li, J., Huang, Z., Zeng, Q., Wang, E., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2021108544 · Cited by 28
tRNA Biology in the Pathogenesis of Diabetes: Role of Genetic and Environmental Factors
Arroyo, M. N., Green, J. A., Cnop, M., & Igoillo‐Esteve, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020496 · Cited by 27
“The deleterious effect of 5′-tRNAGln fragments generated in TRMT10A-deficient pancreatic β-cells [53], as well as the high fat feeding-induced tRHs that contribute to the nongenetic inheritance of metabolic traits [30,55,213,215] highlight the importance of tRNA fragmentation on cell functionality.”
BackgroundInfluentialDysregulation of tRNA methylation in cancer: Mechanisms and targeting therapeutic strategies
Yuan, W., Zhang, R., Lyu, H., Xiao, S., Guo, D., Zhang, Q., Ali, D. W., Michalak, M., Chen, X., Zhou, C., et al. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-02097-x · Cited by 26
Biological function molecular pathways and druggability of DNMT2/TRDMT1.
Li, H., Liu, H.-R., Zhu, D., Dou, C., Gang, B., Zhang, M., & Wan, Z. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107222 · Cited by 24
TRDMT1-mediated RNA C-5 methylation as a novel target in anticancer therapy
Lewińska, A., Adamczyk‐Grochala, J., & Wnuk, M. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.188964 · Cited by 23
Lucky, A. B., Wang, C. C. Q., Li, X., Chim-Ong, A., Adapa, S. R., Quinlivan, E. P., Jiang, R. H. Y., Cui, L., & Miao, J. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad248 · Cited by 28
Self-citationSchwickert, M., Fischer, T. R., Zimmermann, R. A., Hoba, S. N., Meidner, J. L., Weber, M., Weber, M., Stark, M. M., Koch, J., Jung, N., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00388 · Cited by 37
Self-citationTransfer RNA-Derived Small RNAs: Novel Regulators and Biomarkers of Cancers
Fu, B.-F., & Xu, C. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.843598 · Cited by 29
“Thus they protect tRNAs from cleavage into tsRNAs in mice (49).”
BackgroundHypoxia-induced alteration of RNA modifications in the mouse testis and sperm
He, T., Guo, H., Shen, X., Wu, X., Lin, X., Jiang, X., Xu, Y., Chen, D., Zhang, Y., Tan, D., et al. (2021) · Biology of Reproduction · doi:10.1093/biolre/ioab142 · Cited by 34
Self-citationEarly life stress affects the miRNA cargo of epididymal extracellular vesicles in mouse
Alshanbayeva, A., Tanwar, D. K., Roszkowski, M., Manuella, F., & Mansuy, I. M. (2021) · Biology of Reproduction · doi:10.1093/biolre/ioab156 · Cited by 27
“Small RNAs, like tRNAderived fragments (tRFs), miRNAs and more recently rRNA-derived small RNA fragments are believed to act as messengers of a father’s experiences that can be transferred to the offspring [2, 14, 18, 19].”
BackgroundSun, X., Yang, J., Yu, M., Yao, D., Zhou, L., Li, X., Qiu, Q., Lin, W., Lü, B., Chen, E., et al. (2020) · NAR Cancer · doi:10.1093/narcan/zcaa031 · Cited by 24
Self-citationSwanson, G., Estill, M. S., Diamond, M. P., Legro, R. S., Coutifaris, C., Barnhart, K. T., Huang, H., Hansen, K. R., Trussell, J. C., Coward, R. M., et al. (2019) · Epigenetics · doi:10.1080/15592294.2019.1644880 · Cited by 28
Grosso, J. B., Zoff, L., Calvo, K. L., Maraval, M. B., Perez, M., Carbonaro, M., Brignardello, C., Morente, C., & Spinelli, S. V. (2021) · Molecular Human Reproduction · doi:10.1093/molehr/gaab017 · Cited by 22
The epitranscriptome of long noncoding RNAs in metabolic diseases
Yin, L., Zhu, X., Novák, P., Zhou, L., Gao, L., Yang, M., Zhao, G., & Yin, K. (2021) · Clinica Chimica Acta · doi:10.1016/j.cca.2021.01.001 · Cited by 28
Epididymal small non‐coding RNA studies: progress over the past decade
Chu, C., Zhang, Y., Lu, Y., Sharma, S., Fei, Z., & Drevet, J. R. (2019) · Andrology · doi:10.1111/andr.12639 · Cited by 29
“…and play different roles with their well-documented counterpart in the testis; 4. the epididymis functions in mediating not only the content of sperm sncRNAs, but also the modifications to their molecules, as an additional layer of sncRNA dynamics and functional indications (Zhang et al., 2018).”
BackgroundInfluentialSelf-citationEpigenetic Echoes: Bridging Nature, Nurture, and Healing Across Generations
Banushi, B., Collova, J. R., & Milroy, H. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26073075 · Cited by 30
“…experiences rapid, active DNA demethylation coupled with the replacement of protamines by histones, while the maternal genome undergoes slower passive demethylation and histone remodeling, gradually establishing an open chromatin state essential for embryonic development [19,27,92,115,128,154].”
tRNA-derived small RNAs in disease immunity
Jia, H.-Y., & Zhang, L. (2025) · Theranostics · doi:10.7150/thno.102650 · Cited by 21
“For instance, the m5C38 modification of target tRNAs by DNMT2 can reduce the generation of 5' tRNA halves under stress [39, 40].”
Self-citationtRNA and tsRNA: From Heterogeneity to Multifaceted Regulators
Li, Y., Yu, Z., Jiang, W., Lyu, X., Guo, A., Sun, X., Yang, Y.-T., & Zhang, Y. (2024) · Biomolecules · doi:10.3390/biom14101340 · Cited by 21
Self-citationXu, W.-L., Yu, M.-X., Wu, Y.-K., Jie, Y., Li, X.-Y., Zeng, X., Yang, F.-J., & Chong, Y. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.923300 · Cited by 21
“However, rsRNAs show a sensitive response to pathophysiological conditions (Zhang et al., 2018), and the combination of miRNA, tsRNA, and rsRNA in HBV-ACLF has not been reported.”
BackgroundSelf-citationtiRNA-Val promotes angiogenesis via Sirt1–Hif-1α axis in mice with diabetic retinopathy
Xu, Y., Zou, H., Ding, Q., Zou, Y., Tang, C. Y., Lu, Y., & Xu, X. (2022) · Biological Research · doi:10.1186/s40659-022-00381-7 · Cited by 23
“Northern blotting 179 Northern blotting for specific detection of small RNA was performed as previously 180 described(18).”
MethodRNA modifications: emerging players in the regulation of reproduction and development
Wen, J., Zhu, Q., Liu, Y., & Gou, L. (2024) · Acta Biochimica et Biophysica Sinica · doi:10.3724/abbs.2024201 · Cited by 20
Self-citationPaternal hypercholesterolemia elicits sex-specific exacerbation of atherosclerosis in offspring
Hernandez, R., Li, X., Shi, J., Dave, T. R., Zhou, T., Chen, Q., & Zhou, C. (2024) · JCI Insight · doi:10.1172/jci.insight.179291 · Cited by 23
“Many sperm tsRNAs/rsRNAs are highly modified, and these RNA modifications may shape the RNA secondary structures and biological properties to mediate epigenetic inheritance (14, 38, 99).”
BackgroundInfluentialSelf-citationSalehi, M., Kamali, M. J., Rajabzadeh, A., Minoo, S., Mosharafi, H., Saeedi, F., & Daraei, A. (2024) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2024.109930 · Cited by 23
Alteration of RNA modification signature in human sperm correlates with sperm motility
Guo, H., Shen, X., Hu, H., Zhou, P., He, T., Lin, X., Tan, D., Zhang, X., & Zhang, Y. (2022) · Molecular Human Reproduction · doi:10.1093/molehr/gaac031 · Cited by 29
“…marks, which have been implicated in regulating mRNA translational efficiency (Ontiveros et al., 2020), paternally acquired epigenetic inheritance (Zhang et al., 2018) and human tumorigenesis (Chen et al., 2021a), adding complexity and diversity to the transcriptional and translational regulation…”
BackgroundMethodInfluentialSelf-citationAdvanced paternal age increased metabolic risks in mice offspring
Mao, Y., Zhao, Y., Luo, S., Chen, H., Liu, X., Wu, T., Ding, G., Liu, X., Sheng, J., Meng, Y., et al. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2022.166355 · Cited by 19
Plant transfer RNA‐derived fragments: Biogenesis and functions
Ma, X., Liu, C., & Cao, X. (2021) · Journal of Integrative Plant Biology · doi:10.1111/jipb.13143 · Cited by 29
Optimized identification and characterization of small RNAs with PANDORA-seq
Shi, J., Zhang, Y., Li, Y., Zhang, L., Zhang, X., Yan, M., Chen, Q., & Zhang, Y. (2025) · Nature Protocols · doi:10.1038/s41596-025-01158-4 · Cited by 20
Self-citationSmall RNAs: An expanding world with therapeutic promises
Gou, L., Zhu, Q., & Liu, M. (2023) · Fundamental Research · doi:10.1016/j.fmre.2023.03.003 · Cited by 22
“Loss of DNMT2 leads to dysregulation of tsRNAs and rsRNAs in spermatozoa, and in turn, impairs the transmission of diet-induced metabolic disorders [44] .”
BackgroundSrivastava, R., & Lodhi, N. (2022) · Biomolecules · doi:10.3390/biom12030417 · Cited by 22
“Based on genetic factors, DNMT2/TRDMT1-dependent RNA modifications are important in determining the coding signature of sperm small non-coding RNA, which is required for paternal epigenetic memory and in the transmission of paternally acquired metabolic diseases to offspring [44,55].”
BackgroundZeng, L., Zhou, J., Zhang, Y., Wang, X., Wang, M., & Su, P. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.791784 · Cited by 21
Self-citationGerm Granules Allow Transmission of Small RNA-Based Parental Responses in the “Germ Plasm”
Lev, I., & Rechavi, O. (2020) · iScience · doi:10.1016/j.isci.2020.101831 · Cited by 18
NRF2 loss recapitulates heritable impacts of paternal cigarette smoke exposure
Murphy, P. J., Guo, J., Jenkins, T. G., James, E. R., Hoidal, J. R., Huecksteadt, T. P., Broberg, D. S., Hotaling, J. M., Alonso, D., Carrell, D. T., et al. (2020) · PLoS Genetics · doi:10.1371/journal.pgen.1008756 · Cited by 23
Auboeuf, D. (2020) · Life · doi:10.3390/life10020007 · Cited by 22
“underlines the plasticity associated with epigenetic mechanisms [185,186].”
BackgroundtRNA modifications and tRNA-derived small RNAs: new insights of tRNA in human disease
Wu, D., Li, X., Khan, F. A., Yuan, C., Pandupuspitasari, N. S., Huang, C., Sun, F., & Guan, K. (2024) · Cell Biology and Toxicology · doi:10.1007/s10565-024-09919-9 · Cited by 24
“Importantly, Dnmt2 relocates into stress granules under stress conditions and its depletion is known to reduce tRNA stability, and thus promoting biogenesis of tRNA-derived fragments (Schaefer et al. 2009; Zhang et al. 2018).”
InfluentialSelf-citationFather’s diet influences son’s metabolic health through sperm RNA
Cai, C., & Chen, Q. (2024) · Nature · doi:10.1038/d41586-024-01502-w · Cited by 18
Self-citationKobayashi, A., Takeiwa, T., Ikeda, K., & Inoue, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119414 · Cited by 23
Li, H., Wan, X., Zhao, J., Liang, X., Dai, Y., & Li, H. (2022) · Translational research · doi:10.1016/j.trsl.2022.12.006 · Cited by 18
Profiling of miRNAs in porcine Sertoli cells
Chen, X., Zheng, Y., Li, X., Gao, Q., Feng, T., Zhang, P., Liao, M., Tian, X., Lu, H., & Zeng, W. (2020) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-020-00487-6 · Cited by 18
“to reflect the low protein diet and high fat diet stress, which mediate intergenerational inheritance [56, 57].”
BackgroundSelf-citationExploring the impact of environmental factors on male reproductive health through epigenetics
Zhang, Y., Song, J., & Sun, Z. (2025) · Reproductive Toxicology · doi:10.1016/j.reprotox.2025.108832 · Cited by 15
Self-citationTransfer RNA-derived small RNAs (tsRNAs) in gastric cancer
Gan, L., Song, H., & Ding, X. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1184615 · Cited by 16
“DNMT2, altered the sperm small RNA expression profile, including levels of tsRNAs and rsRNAs, and abolished sperm small ncRNAmediated transmission of high-fat-diet-induced metabolic disorders to offspring (45).”
BackgroundKorgan, A. C., Foxx, C. L., Hashmi, H., Sago, S. A., Stamper, C. E., Heinze, J. D., O’Leary, M. E., King, J. L., Perrot, T. S., Lowry, C. A., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-14095-z · Cited by 21
van Calker, D., & Serchov, T. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.03.019 · Cited by 19
Simultaneous profiling of ac4C and m5C modifications from nanopore direct RNA sequencing.
Wu, Y., Shao, W.-N., Liu, S., Wang, L.-Y., Xu, P., Zhang, X.-P., Song, H., Li, X., Wang, J., & Yu, X. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.140863 · Cited by 15
Self-citationChamproux, A., Tang, Y., Dickson, D. A., Meng, A., Harrington, A. N., Liaw, L., Marzi, M. J., Nicassio, F., Schlaeger, T. M., & Feig, L. A. (2024) · Epigenetics · doi:10.1080/15592294.2024.2346694 · Cited by 25
Apomixis: oh, what a tangled web we have!
Terzaroli, N., Anderson, A. W., & Albertini, E. (2023) · Planta · doi:10.1007/s00425-023-04124-0 · Cited by 17
“In addition, several kinds of small RNAs operate against viruses and Transposable Elements (TEs), performing critical functions in development, stress responses, and transgenerational inheritance (Zhang et al. 2018).”
BackgroundChemical Space Virtual Screening against Hard-to-Drug RNA Methyltransferases DNMT2 and NSUN6
Zimmermann, R. A., Fischer, T. R., Schwickert, M., Nidoieva, Z., Schirmeister, T., & Kersten, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076109 · Cited by 18
Modern physiology vindicates Darwin's dream
Noble, D. (2022) · Experimental Physiology · doi:10.1113/ep090133 · Cited by 18
“Good examples of functional transmission of soma characteristics include the work of Zhang et al. (2018) identifying the nucleotide sequences that transmit paternally acquired metabolic disorders, and Toker et al. (2022) showing the transgenerational inheritance of sexual attractiveness in C.…”
BackgroundA Twist between ROS and Sperm-Mediated Intergenerational Epigenetic Inheritance
Zhang, X., & Chen, Q. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.04.003 · Cited by 16
“2) ROS mediate the cleavage of tRNA into tsRNAs (Thompson and Parker, 2009), which depends on factors including tRNA modifications (Zhang et al., 2018), the specific RNases, and the compartmentalization of tRNAs (e.”
BackgroundInfluentialSelf-citationThe Sperm Epigenome: Implications for Assisted Reproductive Technologies
Carrell, D. T. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-21664-1_3 · Cited by 21
Wu, Y., Wei, Y., Li, Y., Dou, Y., Yang, Y., Liu, H., Wang, X., Wang, Z., Su, J., Zhang, Y., et al. (2025) · Advanced Science · doi:10.1002/advs.202414325 · Cited by 13
Self-citationFuture in the past: paternal reprogramming of offspring phenotype and the epigenetic mechanisms
Wu, D., Zhang, K., Guan, K., Khan, F. A., Pandupuspitasari, N. S., Negara, W., Sun, F., & Huang, C. (2024) · Archives of Toxicology · doi:10.1007/s00204-024-03713-6 · Cited by 20
“For example, deletion of Dnmt2, a tRNA methyltransferase, impedes the paternal high-fat-diet (HFD)-induced m 5 C and m 2 G modifications in sperm tsRNA and prevents paternal HFD-induced intergenerational effects (Zhang et al. 2018).”
Metadata
- Authors
- Zhang, Y., Zhang, X., Shi, J., Tuorto, F., Li, X., Liu, Y., Liebers, R., Zhang, L., Qu, Y., Qian, J., Pahima, M., Liu, Y., Yan, M., Cao, Z., Lei, X., Cao, Y., Peng, H., Liu, S., Wang, Y., Zheng, H., Woolsey, R., Quilici, D., Zhai, Q., Li, L., Zhou, T., Yan, W., Lyko, F., Zhang, Y., Zhou, Q., Duan, E., & Chen, Q.
- Affiliations
- University of Nevada, Reno (US)
- German Cancer Research Center (DE)
- Chinese Academy of Sciences (CN)
- Shandong University of Technology (CN)
- Corresponding author
- Zhang, Ying
- Zhou, Qi
- Duan, Enkui
- Chen, Qi
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2018-04-25
- Volume
- 20
- Issue
- 5
- Pages
- 535-540
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC5926820
- OpenAlex
- W2802402149
- Cited by
- 468
- References
- 50
- Citations by year
- 2026: 43 · 2025: 59 · 2024: 50 · 2023: 67 · 2022: 68 · 2021: 56 · 2020: 62 · 2019: 40 · 2018: 22
- FWCI
- 16.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (P30GM110767, P20GM103440)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD060858, R01HD085506, R01HD092431)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- DNMT2, intergenerational transmission, tRNA-derived small RNAs, rRNA-derived small RNAs, RNA methylation, 5-methylcytosine, high-fat diet, sperm epigenome
- MeSH terms
- Paternal Inheritance, Animals, Blood Glucose, DNA (Cytosine-5-)-Methyltransferases, Insulin, Male, Mice, Inbred C57BL, Nucleic Acid Conformation, Phenotype, Spermatozoa, Structure-Activity Relationship, Biomarkers, Mice, Knockout, Gene Expression Regulation, Developmental, Genetic Predisposition to Disease, Heredity, NIH 3T3 Cells, Epigenesis, Genetic, Glucose Metabolism Disorders, Mice, RNA, Small Untranslated, Diet, High-Fat, Transcriptome, Gene-Environment Interaction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
