posted on 2021-05-03, 18:34authored byNing Song, Jun Luo, Lian Huang, Huibin Tian, Yating Chen, Qiuya He
αS1-Casein (encoded by the CSN1S1 gene) is associated with higher rates of allergy
than other milk protein components for humans. microRNAs (miRNAs)
as small noncoding RNA molecules regulate gene expression and influence
diverse biological processes. However, little is known about the regulation
of milk protein synthesis by miRNAs in ruminants. In this study, we
aim to investigate the regulatory roles of miR-204 family members
(miR-204-5p and miR-211) on αS1-casein in goat mammary
epithelial cells (GMEC). Here, we observed that the CSN1S1 mRNA level is upregulated, while miR-204-5p
and miR-211 (miR-204-5p/-211) abundance is downregulated during peak
lactation compared with middle lactation of dairy goats. We found
that miR-204-5p/-211 synergistically inhibit αS1-casein
expression via directly binding to the 3′-untranslated region
(3′UTR) of CSN1S1 in GMEC.
miR-204-5p/-211 increase β-casein mRNA (CSN2) and protein abundance, as well as the signal transducer and activator
of transcription 5a (STAT5a) activity. Further, miR-204-5p/-211 enhance
β-casein expression via the CSN1S1-STAT5a signaling axis and promote β-casein transcription
by activating the STAT5 response element located in the CSN2 promoter. In conclusion, miR-204-5p/-211 regulate αS1-casein and β-casein synthesis via targeting CSN1S1 in GMEC, which provide the strategy for manipulating
miR-204 family members to reduce milk allergy potential and improve
ruminant milk quality for human consumption.