Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals
Open accessAbstract
Offspring affected by sperm small RNAs: Paternal dietary conditions in mammals influence the metabolic phenotypes of offspring. Although prior work suggests the involvement of epigenetic pathways, the mechanisms remains unclear. Two studies now show that altered paternal diet affects the level of small RNAs in mouse sperm. Chen et al. injected sperm transfer RNA (tRNA) fragments from males that had been kept on a high-fat diet into normal oocytes. The progeny displayed metabolic disorders and concomitant alteration of genes in metabolic pathways. Sharma et al. observed the biogenesis and function of small tRNA-derived fragments during sperm maturation. Further understanding of the mechanisms by which progeny are affected by parental exposure may affect human diseases such as diet-induced metabolic disorders. Science , this issue p. 397 , p. 391
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5' fragments of tRNA Gly(GCC) functionally suppress gene expression related to the endogenous retroelement MERVL in mature mouse sperms.
“For example, 5Ј fragments of tRNA Gly(GCC) functionally suppress gene expression related to the endogenous retroelement MERVL in mature mouse sperms (92).”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [92]
The Results report that tRF-Gly-GCC represses MERVL-associated genes in embryonic stem cells and that embryos generated with mature cauda sperm express MERVL targets at lower levels. The paper does not show suppression of those genes in mature sperm themselves; mature sperm are the source of the fragments, while the reported gene-expression effects occur in cells and embryos. (LLM, conf=0.89)
Experimental — accuracy not yet measuredMany tRF-5 molecules have been shown to play modulatory roles in the replication of retroelements.
“Many tRF-5 molecules have recently been shown to play modulatory roles in the replication of retroelements.”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [92]
The Results (page not provided) show that one 5′ tRNA fragment, tRF-Gly-GCC, regulates transcription driven by the MERVL retroelement and represses MERVL-associated genes. They do not show that many tRF-5 molecules modulate retroelement replication; the measured outcome was gene expression, not replication. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSperm-derived mtRNA can respond to environmental cues and affect subsequent offspring development and health trajectories.
“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 [35]
The Results (page unavailable) show that a low-protein paternal diet changes sperm tRNA fragments and that sperm RNA can alter gene expression in early mouse embryos. The paper does not identify these fragments as mtRNA, and it says whether the embryonic changes cause later metabolic consequences remains undetermined. Thus it supports an environmental response and an early developmental effect, but not the full claim about mtRNA and offspring health trajectories. (LLM, conf=0.85)
Experimental — accuracy not yet measuredtRNA fragments repress genes associated with endogenous retroelements.
“The effectors of these perturbations are DNA methylation, Polycomb components, and transfer RNA (tRNA) fragments, which, among other effects, repress genes associated with endogenous retroelements and might thereby help to preserve genome integrity [87][88][89] .”
From Advances in epigenetics link genetics to the environment and disease (2019) · cites this paper as [87]
DNA methylation, Polycomb components, and tRNA fragments are effectors of these metabolic perturbations.
“The effectors of these perturbations are DNA methylation, Polycomb components, and transfer RNA (tRNA) fragments, which, among other effects, repress genes associated with endogenous retroelements and might thereby help to preserve genome integrity [87][88][89] .”
From Advances in epigenetics link genetics to the environment and disease (2019) · cites this paper as [87]
Repression of endogenous retroelement-associated genes by tRNA fragments might help preserve genome integrity.
“The effectors of these perturbations are DNA methylation, Polycomb components, and transfer RNA (tRNA) fragments, which, among other effects, repress genes associated with endogenous retroelements and might thereby help to preserve genome integrity [87][88][89] .”
From Advances in epigenetics link genetics to the environment and disease (2019) · cites this paper as [87]
Metabolic changes can affect specific loci and produce long-lasting epigenetic modifications, including intergenerational epigenetic inheritance.
“On the other hand, metabolic changes can affect specific loci and induce long-lasting epigenetic modifications, including intergenerational epigenetic inheritance [85][86][87] .”
From Advances in epigenetics link genetics to the environment and disease (2019) · cites this paper as [87]
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- Authors
- 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., Song, L., Carone, B. R., Ricci, E. P., Li, X. Z., Fauquier, L., Moore, M. J., Sullivan, R., Mello, C. C., Garber, M., & Rando, O. J.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
- Department of Obstetrics, Gynecology and Reproduction, Université Laval, Centre Hospitalier Universitaire de Québec Research Center, Quebec City, Quebec G1V 4G2, Canada.
- Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
- Howard Hughes Medical Institute (US)
- Centre hospitalier universitaire de Québec (CA)
- Corresponding author
- Sharma, Upasna
- Conine, Colin C.
- Rando, Oliver J.
- ORCID
- Venue
- Science
- Published
- 2016-01-22
- Volume
- 351
- Issue
- 6271
- Pages
- 391-396
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4888079
- OpenAlex
- W2201382378
- Cited by
- 1,275
- References
- 20
- Citations by year
- 2026: 82 · 2025: 107 · 2024: 118 · 2023: 112 · 2022: 125 · 2021: 141 · 2020: 152 · 2019: 113 · 2018: 135 · 2017: 104 · 2016: 83 · 2015: 1
- FWCI
- 121.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- eScholarship@UMassChan (submittedVersion)
- Funders
- NIH (R01HD080224, DP1ES025458)
- March of Dimes (FY13-1268)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- tRNA-derived fragments, sperm maturation, epididymis, epididymosomes, small RNA biogenesis, paternal diet, protein restriction, let-7 microRNA, glycine tRNA, endogenous retroelements, MERVL, preimplantation embryo, transgenerational epigenetic inheritance
- MeSH terms
- Animals, Blastocyst, Epididymis, Fertilization, Gene Expression Regulation, Male, RNA, Transfer, Gly, Sperm Maturation, Spermatozoa, Testis, Retroelements, Diet, Protein-Restricted, MicroRNAs, Mice
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