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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

RNAi-facilitating features of C. elegans. A: Uptake of dsRNA from the environment is allowed in part by the action of transmembrane protein SID-1, promoting endocytosis of bound RNA. B: RNAi amplification. dsRNA molecules are processed to short “primary” siRNA (left). When an siRNA molecule binds to a target, additional target-complementary siRNAs can be generated after extension by RNA-dependent RNA polymerase and processing. C: SID-2 binds long dsRNA for endocytosis and secondary uptake into the cytoplasm by SID-1 (not shown). Note that cartoons are for illustration only and are not meant to represent relative size or molecular topology.
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fig01: RNAi-facilitating features of C. elegans. A: Uptake of dsRNA from the environment is allowed in part by the action of transmembrane protein SID-1, promoting endocytosis of bound RNA. B: RNAi amplification. dsRNA molecules are processed to short “primary” siRNA (left). When an siRNA molecule binds to a target, additional target-complementary siRNAs can be generated after extension by RNA-dependent RNA polymerase and processing. C: SID-2 binds long dsRNA for endocytosis and secondary uptake into the cytoplasm by SID-1 (not shown). Note that cartoons are for illustration only and are not meant to represent relative size or molecular topology.

Mentions: In C. elegans, long dsRNA injected into one part of the organism exert silencing effects in remote locations [9]. A transmembrane protein channel for dsRNA (Fig. 1A), dubbed SID-1 after a ‘systemic RNAi-deficient’ genomic locus identified in screens, is responsible [10–12]. Conservation of this channel indicated the possibility of systemic dissemination of dsRNA in many other organisms [11]. Some form of systemic RNAi exists in organisms ranging from the honeybee [13] and the flour beetle [14] to planarian flatworms [15]. However, long-range RNA transfer does not occur in the same way in vertebrates, which have developed mechanisms to recognize both single- and double-stranded RNA and its features, thereby triggering powerful innate immune responses [16–21]. Even in C. elegans, dsRNA distribution may not apply equally to RNA molecules of different size or type, as dsRNA of 100 nucleotides or longer are the best silencing effectors [22,23]. This is due in part to preferential uptake of longer double-stranded molecules by SID-1 [24]. Transfer of double-stranded precursors by SID-1 may, however, result in cytoplasmic presence of single-stranded RNA species [12].


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)

RNAi-facilitating features of C. elegans. A: Uptake of dsRNA from the environment is allowed in part by the action of transmembrane protein SID-1, promoting endocytosis of bound RNA. B: RNAi amplification. dsRNA molecules are processed to short “primary” siRNA (left). When an siRNA molecule binds to a target, additional target-complementary siRNAs can be generated after extension by RNA-dependent RNA polymerase and processing. C: SID-2 binds long dsRNA for endocytosis and secondary uptake into the cytoplasm by SID-1 (not shown). Note that cartoons are for illustration only and are not meant to represent relative size or molecular topology.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig01: RNAi-facilitating features of C. elegans. A: Uptake of dsRNA from the environment is allowed in part by the action of transmembrane protein SID-1, promoting endocytosis of bound RNA. B: RNAi amplification. dsRNA molecules are processed to short “primary” siRNA (left). When an siRNA molecule binds to a target, additional target-complementary siRNAs can be generated after extension by RNA-dependent RNA polymerase and processing. C: SID-2 binds long dsRNA for endocytosis and secondary uptake into the cytoplasm by SID-1 (not shown). Note that cartoons are for illustration only and are not meant to represent relative size or molecular topology.
Mentions: In C. elegans, long dsRNA injected into one part of the organism exert silencing effects in remote locations [9]. A transmembrane protein channel for dsRNA (Fig. 1A), dubbed SID-1 after a ‘systemic RNAi-deficient’ genomic locus identified in screens, is responsible [10–12]. Conservation of this channel indicated the possibility of systemic dissemination of dsRNA in many other organisms [11]. Some form of systemic RNAi exists in organisms ranging from the honeybee [13] and the flour beetle [14] to planarian flatworms [15]. However, long-range RNA transfer does not occur in the same way in vertebrates, which have developed mechanisms to recognize both single- and double-stranded RNA and its features, thereby triggering powerful innate immune responses [16–21]. Even in C. elegans, dsRNA distribution may not apply equally to RNA molecules of different size or type, as dsRNA of 100 nucleotides or longer are the best silencing effectors [22,23]. This is due in part to preferential uptake of longer double-stranded molecules by SID-1 [24]. Transfer of double-stranded precursors by SID-1 may, however, result in cytoplasmic presence of single-stranded RNA species [12].

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