E2F1-miR-20a-5p/20b-5p auto-regulatory feedback loop involved in myoblast proliferation and differentiation.
miR-17 family microRNAs (miRNAs) are crucial for embryo development, however, their role in muscle development is still unclear. miR-20a-5p and miR-20b-5p belong to the miR-17 family and are transcribed from the miR-17~92 and miR-106a~363 clusters respectively. In this study, we found that miR-20a-5p and miR-20b-5p promoted myoblast differentiation and repressed myoblast proliferation by directly binding the 3' UTR of E2F transcription factor 1 (E2F1) mRNA. E2F1 is an important transcriptional factor for organism's normal development. Overexpression of E2F1 in myoblasts promoted myoblast proliferation and inhibited myoblast differentiation. Conversely, E2F1 inhibition induced myoblast differentiation and repressed myoblast proliferation. Moreover, E2F1 can bind directly to promoters of the miR-17~92 and miR-106a~363 clusters and activate their transcription, and E2F1 protein expression is correlated with the expression of pri-miR-17~92 and pri-miR-106a~363 during myoblast differentiation. These results suggested an auto-regulatory feedback loop between E2F1 and miR-20a-5p/20b-5p, and indicated that miR-20a-5p, miR-20b-5p and E2F1 are involved in myoblast proliferation and differentiation through the auto-regulation between E2F1 and miR-20a-5p/20b-5p. These findings provide new insight into the mechanism of muscle differentiation, and further shed light on the understanding of muscle development and muscle diseases.
Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong Province, China.|Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, South China Agricultural University, Guangzhou 510642, Guangdong Province, China.
Wen
W
Luo
Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong Province, China.|Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, South China Agricultural University, Guangzhou 510642, Guangdong Province, China.
Guihuan
G
Li
Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong Province, China.|Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, South China Agricultural University, Guangzhou 510642, Guangdong Province, China.
Zhenhua
Z
Yi
Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong Province, China.|Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, South China Agricultural University, Guangzhou 510642, Guangdong Province, China.
Qinghua
Q
Nie
Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong Province, China.|Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, South China Agricultural University, Guangzhou 510642, Guangdong Province, China.
Xiquan
X
Zhang
D020413:3' Untranslated Regions; D000818:Animals; D000070416:Antagomirs / Q000378:metabolism; D001483:Base Sequence; D059447:Cell Cycle Checkpoints; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002645:Chickens; D050687:E2F1 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016415:Sequence Alignment
D020413:3' Untranslated Regions; D000070416:Antagomirs; D050687:E2F1 Transcription Factor; D035683:MicroRNAs; D017570:MyoD Protein; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018995:Myosin Heavy Chains