Abstract
MicroRNAs have been long considered synthesized endogenously until very recent discoveries showing that human can absorb dietary microRNAs from animal and plant origins while the mechanism remains unknown. Compelling evidences of microRNAs from rice, milk, and honeysuckle transported to human blood and tissues have created a high volume of interests in the fundamental questions that which and how exogenous microRNAs can be transferred into human circulation and possibly exert functions in humans. Here we present an integrated genomics and computational analysis to study the potential deciding features of transportable microRNAs. Specifically, we analyzed all publicly available microRNAs, a total of 34,612 from 194 species, with 1,102 features derived from the microRNA sequence and structure. Through in-depth bioinformatics analysis, 8 groups of discriminative features have been used to characterize human circulating microRNAs and infer the likelihood that a microRNA will get transferred into human circulation. For example, 345 dietary microRNAs have been predicted as highly transportable candidates where 117 of them have identical sequences with their homologs in human and 73 are known to be associated with exosomes. Through a milk feeding experiment, we have validated 9 cow-milk microRNAs in human plasma using microRNA-sequencing analysis, including the top ranked microRNAs such as bta-miR-487b, miR-181b, and miR-421. The implications in health-related processes have been illustrated in the functional analysis. This work demonstrates the data-driven computational analysis is highly promising to study novel molecular characteristics of transportable microRNAs while bypassing the complex mechanistic details.
Highlights
Mature microRNAs are a class of short non-coding RNAs, 21–25 nucleotides in length and endogenously transcribed in animals, plants, and viruses
It was very recently discovered that humans absorb a meaningful amount of certain exosomal miRNAs from cow’s milk, e.g., miR-29b and 200c; the endogenous miRNA synthesis does not compensate for dietary deficiency [5]; the biogenesis and function of such exogenous miRNAs are health related [5,6,7,8]
While the evidence in support of milk-miRNA bioavailability is unambiguous, a recent report that mammals can absorb plant miRNAs from rice [9], was met with widespread skepticism [10,11,12,13]. Based on these evidences, challenging questions may be raised regarding how human pick up miRNAs from dietary intake, why some exogenous miRNAs can be transferred into human circulation while others cannot, and what are the broader functional roles played by exogenous miRNAs in human disease processes
Summary
Mature microRNAs (miRNAs) are a class of short non-coding RNAs, 21–25 nucleotides in length and endogenously transcribed in animals, plants, and viruses These small molecules often regulate gene expression post-transcriptionally via base paring with complementary sites. While the evidence in support of milk-miRNA bioavailability is unambiguous, a recent report that mammals can absorb plant miRNAs (e.g. miR-168a) from rice [9], was met with widespread skepticism [10,11,12,13] Based on these evidences, challenging questions may be raised regarding how human pick up miRNAs from dietary intake, why some exogenous miRNAs can be transferred into human circulation while others cannot, and what are the broader functional roles played by exogenous miRNAs in human disease processes
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