MicroRNA 26b encoded by the intron of small CTD phosphatase (SCP) 1 has an antagonistic effect on its host gene.
Tissue-specific patterns of gene expression play an important role in the distinctive features of each organ. Small CTD phosphatases (SCPs) 1-3 are recruited by repressor element 1 (RE-1)-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells. SCPs are highly expressed in the heart and contain microRNAs (miR)-26b, 26a-2, and 26a-1 with the same seed sequence in their introns. Therefore, we tried to investigate the roles of miR-26b and its host gene in neonatal rat cardiomyocytes. Overexpression of miR-26b suppressed the mRNA expression levels of ANF, βMHC, and ACTA1 and reduced the cell surface area in cardiomyocytes. We confirmed that miR-26b targets the 3' untranslated region (3'UTR) of GATA4 and canonical transient receptor potential channel (TRPC) 3. Conversely, silencing of the endogenous miR-26b family enhanced the expression levels of TRPC3 and GATA4. On the other hand, overexpression of SCP1 induced the mRNA expression of ANF and βMHC and increased the cell surface area in cardiomyocytes. Next, we compared the effect of overexpression of SCP1 with its introns and SCP1 cDNA to observe the net function of SCP1 expression on cardiac hypertrophy. When the expression levels of SCP1 were the same, the overexpression of SCP1 cDNA had a greater effect at inducing cardiac hypertrophy than SCP1 cDNA with its intron. In conclusion, SCP1 itself has the potential to induce cardiac hypertrophy; however, the effect is suppressed by intronic miR-26b in cardiomyocytes. miR-26b has an antagonistic effect on its host gene SCP1.
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Naoya
N
Sowa
Takahiro
T
Horie
Yasuhide
Y
Kuwabara
Osamu
O
Baba
Shin
S
Watanabe
Hitoo
H
Nishi
Minako
M
Kinoshita
Rieko
R
Takanabe-Mori
Hiromichi
H
Wada
Akira
A
Shimatsu
Koji
K
Hasegawa
Takeshi
T
Kimura
Koh
K
Ono
D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D006332:Cardiomegaly / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D007438:Introns; D008156:Luciferases; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D035683:MicroRNAs; C543693:Mirn26 microRNA, mouse; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C078744:Sycp1 protein, rat; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D009320:Atrial Natriuretic Factor; D008156:Luciferases