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Transfer and functional consequences of dietary microRNAs in vertebrates: concepts in search of corroboration: negative results challenge the hypothesis that dietary xenomiRs cross the gut and regulate genes in ingesting vertebrates, but important questions persist.

Witwer KW, Hirschi KD - Bioessays (2014)

Bottom Line: RNA interference (RNAi) mechanisms of Caenorhabditis elegans are enhanced by uptake of environmental RNA and amplification and systemic distribution of RNAi effectors.In this article, we review the evidence for and against a significant role for dietary miRNAs in influencing gene expression, and make recommendations for future studies.Also watch the Video Abstract.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Comparative Pathobiology, The Johns Hopkins University, Baltimore, MD, USA.

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Related in: MedlinePlus

Extracellular carriers and trans-barrier transport of RNA. A: Extracellular RNA is carried by and protected by incorporation into extracellular vesicles (EV, left) including exosomes, microvesicles, some viruses, and other membrane-bound entities; low-density (middle left) and high-density (middle right) lipoprotein particles; and protein complexes such as Argonaute-containing structures (right). The number of RNA molecules within such carriers is not well known. B: Transcytosis may deliver RNA from one side of a cell barrier to the other. Although uncomplexed RNA is shown here, uptake of RNA carriers is more likely. C: Transfer of RNA molecules via transmembrane channels. Here, a double-stranded species is transferred. D: Immune cells in biological barriers may sample nucleic acids and other molecules on one side and release them on the other, with or without movement of the immune cell to a new location.
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fig03: Extracellular carriers and trans-barrier transport of RNA. A: Extracellular RNA is carried by and protected by incorporation into extracellular vesicles (EV, left) including exosomes, microvesicles, some viruses, and other membrane-bound entities; low-density (middle left) and high-density (middle right) lipoprotein particles; and protein complexes such as Argonaute-containing structures (right). The number of RNA molecules within such carriers is not well known. B: Transcytosis may deliver RNA from one side of a cell barrier to the other. Although uncomplexed RNA is shown here, uptake of RNA carriers is more likely. C: Transfer of RNA molecules via transmembrane channels. Here, a double-stranded species is transferred. D: Immune cells in biological barriers may sample nucleic acids and other molecules on one side and release them on the other, with or without movement of the immune cell to a new location.

Mentions: Given the instability of naked RNA, transcytosis – vesicular uptake of RNA carriers and their cargo (Fig. 3A) on one side and release on the other side of a biological barrier – is an attractive option (Fig. 3B). Alternatively, uptake into the cytoplasm by transmembrane RNA transporters is hypothetically possible (Fig. 3C) but would require close contact with a cell or carrier that releases the RNA in the immediate vicinity of the transporter. Additionally, immune cells could take up RNA/RNA carriers and release them on the other side of the barrier (Fig. 3D).


Transfer and functional consequences of dietary microRNAs in vertebrates: concepts in search of corroboration: negative results challenge the hypothesis that dietary xenomiRs cross the gut and regulate genes in ingesting vertebrates, but important questions persist.

Witwer KW, Hirschi KD - Bioessays (2014)

Extracellular carriers and trans-barrier transport of RNA. A: Extracellular RNA is carried by and protected by incorporation into extracellular vesicles (EV, left) including exosomes, microvesicles, some viruses, and other membrane-bound entities; low-density (middle left) and high-density (middle right) lipoprotein particles; and protein complexes such as Argonaute-containing structures (right). The number of RNA molecules within such carriers is not well known. B: Transcytosis may deliver RNA from one side of a cell barrier to the other. Although uncomplexed RNA is shown here, uptake of RNA carriers is more likely. C: Transfer of RNA molecules via transmembrane channels. Here, a double-stranded species is transferred. D: Immune cells in biological barriers may sample nucleic acids and other molecules on one side and release them on the other, with or without movement of the immune cell to a new location.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109825&req=5

fig03: Extracellular carriers and trans-barrier transport of RNA. A: Extracellular RNA is carried by and protected by incorporation into extracellular vesicles (EV, left) including exosomes, microvesicles, some viruses, and other membrane-bound entities; low-density (middle left) and high-density (middle right) lipoprotein particles; and protein complexes such as Argonaute-containing structures (right). The number of RNA molecules within such carriers is not well known. B: Transcytosis may deliver RNA from one side of a cell barrier to the other. Although uncomplexed RNA is shown here, uptake of RNA carriers is more likely. C: Transfer of RNA molecules via transmembrane channels. Here, a double-stranded species is transferred. D: Immune cells in biological barriers may sample nucleic acids and other molecules on one side and release them on the other, with or without movement of the immune cell to a new location.
Mentions: Given the instability of naked RNA, transcytosis – vesicular uptake of RNA carriers and their cargo (Fig. 3A) on one side and release on the other side of a biological barrier – is an attractive option (Fig. 3B). Alternatively, uptake into the cytoplasm by transmembrane RNA transporters is hypothetically possible (Fig. 3C) but would require close contact with a cell or carrier that releases the RNA in the immediate vicinity of the transporter. Additionally, immune cells could take up RNA/RNA carriers and release them on the other side of the barrier (Fig. 3D).

Bottom Line: RNA interference (RNAi) mechanisms of Caenorhabditis elegans are enhanced by uptake of environmental RNA and amplification and systemic distribution of RNAi effectors.In this article, we review the evidence for and against a significant role for dietary miRNAs in influencing gene expression, and make recommendations for future studies.Also watch the Video Abstract.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Comparative Pathobiology, The Johns Hopkins University, Baltimore, MD, USA.

Show MeSH
Related in: MedlinePlus