Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals

Sharma, Upasna; Conine, Colin C.; Shea, Jeremy; Bošković, Ana; Derr, Alan; Bing, Xin Yang; Belleannée, Clémence; Küçükural, Alper; Serra, Ryan W.; Sun, Fengyun; Song, Lina; Carone, Benjamin R.; Ricci, Emiliano P.; Li, Xin Z.; Fauquier, Lucas; Moore, Melissa J.; Sullivan, Robert; Mello, Craig C.; Garber, Manuel; Rando, Oliver J.

doi:10.1126/science.aad6780

Cited by 1,051 publications

(1,497 citation statements)

References 36 publications

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“…In the new paper published in Science, they used hepatic Squalene epoxidase (Sqle) expression in offspring resulting from IVF as a read-out for successful transmission of a phenotype. Consistent with a previous study [5], they report altered miRNA levels in sperm of males subjected to altered diet, but subsequently focused on tRNA fragments [7] which they found to be the most abundant class of RNA in mature sperm and therefore in their opinion have the highest chance to be functionally relevant in the zygote after fertilization.…”

supporting

confidence: 72%

tRNA fragments: novel players in intergenerational inheritance

Gapp

Miska

2016

Cell Res

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supporting

confidence: 72%

tRNA fragments: novel players in intergenerational inheritance

Gapp

Miska

2016

Cell Res

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“…Alternatively, intergenerational effects could result if RNAs carry sequence-specific information to gametes through circulation from distant tissues that experience chemicals, changes in diet, or stress. In support of this possibility, studies focused on intergenerational and transgenerational effects in mammals implicate RNA in the inheritance of gene expression states across generations (47), report changes in small RNAs in gametes (48,49), and report changes in RNAs acquired during gamete maturation from surrounding epithelia (50,51). However, in all these cases, direct effects of a treatment-e.g., diet-on gametes and surrounding support tissues that alter RNA composition in gametes have not been ruled out.…”

Section: Rnas In Circulation As Carriers Of Gene-specific Informationmentioning

confidence: 99%

Extracellular RNA is transported from one generation to the next in Caenorhabditis elegans

Marre

Traver

Jose

2016

Proc. Natl. Acad. Sci. U.S.A.

107

144

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Experiences during the lifetime of an animal have been proposed to have consequences for subsequent generations. Although it is unclear how such intergenerational transfer of information occurs, RNAs found extracellularly in animals are candidate molecules that can transfer gene-specific regulatory information from one generation to the next because they can enter cells and regulate gene expression. In support of this idea, when double-stranded RNA (dsRNA) is introduced into some animals, the dsRNA can silence genes of matching sequence and the silencing can persist in progeny. Such persistent gene silencing is thought to result from sequencespecific interaction of the RNA within parents to generate chromatin modifications, DNA methylation, and/or secondary RNAs, which are then inherited by progeny. Here, we show that dsRNA can be directly transferred between generations in the worm Caenorhabditis elegans. Intergenerational transfer of dsRNA occurs even in animals that lack any DNA of matching sequence, and dsRNA that reaches progeny can spread between cells to cause gene silencing. Surprisingly, extracellular dsRNA can also reach progeny without entry into the cytosol, presumably within intracellular vesicles. Fluorescently labeled dsRNA is imported from extracellular space into oocytes along with yolk and accumulates in punctate structures within embryos. Subsequent entry into the cytosol of early embryos causes gene silencing in progeny. These results demonstrate the transport of extracellular RNA from one generation to the next to regulate gene expression in an animal and thus suggest a mechanism for the transmission of experience-dependent effects between generations.circulating RNA | parental RNAi | epigenetics | transgenerational inheritance | endocytosis

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“…4,[6][7][8][9][10][11][12][13] It is also increasingly becoming apparent that the environmental state of both the mother and father can underpin later diseases in offspring, even those who appear healthy at birth. [14][15][16][17][18][19][20][21][22][23][24][25][26] Such intrinsic and extrinsic factors in animal models and humans include exposure to endocrine disrupting chemicals, such as bisphenol A, phthalates, heavy metals, stress, obesity, high fat/ high caloric diets, metabolic status and starvation conditions to provide a few examples. It is also clear that in general, males may be at greater risk for later disorders, including those of the cardiovascular and neurological systems, than females.…”

Section: Introductionmentioning

confidence: 99%

Homage to the ‘H’ in developmental origins of health and disease

Rosenfeld

2016

J Dev Orig Health Dis

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Abundant evidence exists linking maternal and paternal environments from pericopconception through the postnatal period to later risk to offspring diseases. This concept was first articulated by the late Sir David Barker and as such coined the Barker Hypothesis. The term was then mutated to Fetal Origins of Adult Disease and finally broadened to developmental origins of adult health and disease (DOHaD) in recognition that the perinatal environment can shape both health and disease in resulting offspring. Developmental exposure to various factors, including stress, obesity, caloric-rich diets and environmental chemicals can lead to detrimental offspring health outcomes. However, less attention has been paid to date on measures that parents can take to promote the long-term health of their offspring. In essence, have we neglected to consider the ‘H’ in DOHaD? It is the ‘H’ component that should be of primary concern to expecting mothers and fathers and those seeking to have children. While it may not be possible to eliminate exposure to all pernicious factors, prevention/remediation strategies may tip the scale to health rather than disease. By understanding disruptive DOHaD mechanisms, it may also illuminate behavioral modifications that parents can adapt before fertilization and throughout the neonatal period to promote the lifelong health of their male and female offspring. Three possibilities will be explored in the current review: parental exercise, probiotic supplementation and breastfeeding in the case of mothers. The ‘H’ paradigm should be the focus going forward as a healthy start can indeed last a lifetime.

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Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals

Cited by 1,051 publications

References 36 publications

tRNA fragments: novel players in intergenerational inheritance

tRNA fragments: novel players in intergenerational inheritance

Extracellular RNA is transported from one generation to the next in Caenorhabditis elegans

Homage to the ‘H’ in developmental origins of health and disease

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