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Food Deprivation Affects the miRNome in the Lactating Goat Mammary Gland.

Mobuchon L, Marthey S, Le Guillou S, Laloë D, Le Provost F, Leroux C - PLoS ONE (2015)

Bottom Line: Among the putative targets, 19 were previously identified as differently expressed genes (DEG).The functions of these 19 DEG revealed, notably, their involvement in tissue remodelling.In conclusion, this study offers the first evidence of nutriregulated miRNA in the ruminant mammary gland.

View Article: PubMed Central - PubMed

Affiliation: INRA, UMR1313 Génétique Animale et Biologie Intégrative, F-78350, Jouy-en-Josas, France; INRA, UMR1213 Herbivores, F-63122, Saint Genès Champanelle, France; Clermont Université, VetAgro Sup, UMR1213 Herbivores, BP 10448, F-63000, Clermont-Ferrand, France.

ABSTRACT

Background: Nutrition affects milk composition thus influencing its nutritional properties. Nutrition also modifies the expression of mammary genes, whose regulation is not fully understood. MicroRNAs (miRNA) are small non coding RNA which are important post-transcriptional regulators of gene expression by targeting messenger RNAs. Our goal was to characterize miRNA whose expression is regulated by nutrition in the lactating goat mammary gland, which may provide clues to deciphering regulations of the biosynthesis and secretion of milk components.

Methodology/principal findings: Using high-throughput sequencing technology, miRNomes of the lactating mammary gland were established from lactating goats fed ad libitum or deprived of food for 48 h affecting milk production and composition. High throughput miRNA sequencing revealed 30 miRNA with an expression potentially modulated by food deprivation; 16 were down-regulated and 14 were up-regulated. Diana-microT predictive tools suggested a potential role for several nutriregulated miRNA in lipid metabolism. Among the putative targets, 19 were previously identified as differently expressed genes (DEG). The functions of these 19 DEG revealed, notably, their involvement in tissue remodelling.

Conclusion/significance: In conclusion, this study offers the first evidence of nutriregulated miRNA in the ruminant mammary gland. Characterization of these 30 miRNA could contribute to a clearer understanding of gene regulation in the mammary gland in response to nutrition.

No MeSH data available.


Nutriregulated miRNA binding sites on ESR1 mRNA.Analyses were performed using DIANA microT v5.0 [36] for miR-125b-3p and miR-222-3p and Custom Target Scan v5.2 [37] for chr19_26739-5p. The interaction between 3’UTR of ESR1 and the seed region of miR-222-3p of one binding site is described in the box.
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pone.0140111.g005: Nutriregulated miRNA binding sites on ESR1 mRNA.Analyses were performed using DIANA microT v5.0 [36] for miR-125b-3p and miR-222-3p and Custom Target Scan v5.2 [37] for chr19_26739-5p. The interaction between 3’UTR of ESR1 and the seed region of miR-222-3p of one binding site is described in the box.

Mentions: Of all the putative targets predicted for nutriregulated miRNA, 47 were among the genes previously identified as being significantly affected (named DEG) by food deprivation using a microarray technique [2] (S5 Table). One to six miRNA were predicted to targets these 47 DEG. In addition, when the way of variations in DEG and nutriregulated miRNA was taken account, 19 DEG were found to be potentially targeted by nutriregulated miRNA, including 18 down-regulated DEG which might be targeted by one to three up-regulated miRNA (Table 4) one up-regulated DEG (CD24) might be targeted by chr3_3319-5p which was down-regulated in FD goats. By investigating the cellular and molecular functions of these 19 DEG, “cellular death and survival”, “cellular morphology” and “cell-to-cell interaction” were found to be among the five most targeted functions (data not shown). This suggests that the deregulation of miRNA may explain the phenotype of mammary tissue remodelling previously hypothesized in FD goats [2]. Among the DEG that may be targeted by three nutriregulated miRNA, ESR1 is a transcription factor that regulates genetic programming of cell cycle progression and growth in the mammary gland. The knockout of ESR1 in mice suggests its crucial role in alveologenesis during lactation [67]. Interestingly, ESR1 was down-regulated by food deprivation and potentially targeted by miR-125b-3p, miR-222-3p, and chr19_26739-5p, and up-regulated in the mammary gland of FD goats. In addition miR-222-3p has been confirmed as directly targeting ESR1 in breast cancer cell lines [68]. Its binding site (Fig 5) is conserved among different species, including cattle and goats. These observations suggest that the up-regulation of miR-222-3p by food deprivation may be responsible for the down-regulation of ESR1.


Food Deprivation Affects the miRNome in the Lactating Goat Mammary Gland.

Mobuchon L, Marthey S, Le Guillou S, Laloë D, Le Provost F, Leroux C - PLoS ONE (2015)

Nutriregulated miRNA binding sites on ESR1 mRNA.Analyses were performed using DIANA microT v5.0 [36] for miR-125b-3p and miR-222-3p and Custom Target Scan v5.2 [37] for chr19_26739-5p. The interaction between 3’UTR of ESR1 and the seed region of miR-222-3p of one binding site is described in the box.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608672&req=5

pone.0140111.g005: Nutriregulated miRNA binding sites on ESR1 mRNA.Analyses were performed using DIANA microT v5.0 [36] for miR-125b-3p and miR-222-3p and Custom Target Scan v5.2 [37] for chr19_26739-5p. The interaction between 3’UTR of ESR1 and the seed region of miR-222-3p of one binding site is described in the box.
Mentions: Of all the putative targets predicted for nutriregulated miRNA, 47 were among the genes previously identified as being significantly affected (named DEG) by food deprivation using a microarray technique [2] (S5 Table). One to six miRNA were predicted to targets these 47 DEG. In addition, when the way of variations in DEG and nutriregulated miRNA was taken account, 19 DEG were found to be potentially targeted by nutriregulated miRNA, including 18 down-regulated DEG which might be targeted by one to three up-regulated miRNA (Table 4) one up-regulated DEG (CD24) might be targeted by chr3_3319-5p which was down-regulated in FD goats. By investigating the cellular and molecular functions of these 19 DEG, “cellular death and survival”, “cellular morphology” and “cell-to-cell interaction” were found to be among the five most targeted functions (data not shown). This suggests that the deregulation of miRNA may explain the phenotype of mammary tissue remodelling previously hypothesized in FD goats [2]. Among the DEG that may be targeted by three nutriregulated miRNA, ESR1 is a transcription factor that regulates genetic programming of cell cycle progression and growth in the mammary gland. The knockout of ESR1 in mice suggests its crucial role in alveologenesis during lactation [67]. Interestingly, ESR1 was down-regulated by food deprivation and potentially targeted by miR-125b-3p, miR-222-3p, and chr19_26739-5p, and up-regulated in the mammary gland of FD goats. In addition miR-222-3p has been confirmed as directly targeting ESR1 in breast cancer cell lines [68]. Its binding site (Fig 5) is conserved among different species, including cattle and goats. These observations suggest that the up-regulation of miR-222-3p by food deprivation may be responsible for the down-regulation of ESR1.

Bottom Line: Among the putative targets, 19 were previously identified as differently expressed genes (DEG).The functions of these 19 DEG revealed, notably, their involvement in tissue remodelling.In conclusion, this study offers the first evidence of nutriregulated miRNA in the ruminant mammary gland.

View Article: PubMed Central - PubMed

Affiliation: INRA, UMR1313 Génétique Animale et Biologie Intégrative, F-78350, Jouy-en-Josas, France; INRA, UMR1213 Herbivores, F-63122, Saint Genès Champanelle, France; Clermont Université, VetAgro Sup, UMR1213 Herbivores, BP 10448, F-63000, Clermont-Ferrand, France.

ABSTRACT

Background: Nutrition affects milk composition thus influencing its nutritional properties. Nutrition also modifies the expression of mammary genes, whose regulation is not fully understood. MicroRNAs (miRNA) are small non coding RNA which are important post-transcriptional regulators of gene expression by targeting messenger RNAs. Our goal was to characterize miRNA whose expression is regulated by nutrition in the lactating goat mammary gland, which may provide clues to deciphering regulations of the biosynthesis and secretion of milk components.

Methodology/principal findings: Using high-throughput sequencing technology, miRNomes of the lactating mammary gland were established from lactating goats fed ad libitum or deprived of food for 48 h affecting milk production and composition. High throughput miRNA sequencing revealed 30 miRNA with an expression potentially modulated by food deprivation; 16 were down-regulated and 14 were up-regulated. Diana-microT predictive tools suggested a potential role for several nutriregulated miRNA in lipid metabolism. Among the putative targets, 19 were previously identified as differently expressed genes (DEG). The functions of these 19 DEG revealed, notably, their involvement in tissue remodelling.

Conclusion/significance: In conclusion, this study offers the first evidence of nutriregulated miRNA in the ruminant mammary gland. Characterization of these 30 miRNA could contribute to a clearer understanding of gene regulation in the mammary gland in response to nutrition.

No MeSH data available.