Histone deacetylase 1 enhances microRNA processing via deacetylation of DGCR8.
Relatively little is known about the regulatory mechanisms of the Drosha/DGCR8 complex, which processes miRNAs at the initial step of biogenesis. We found that histone deacetylase 1 (HDAC1) increases the expression levels of mature miRNAs despite repressing the transcription of host genes. HDAC1 is an integral component of the Drosha/DGCR8 complex and enhances miRNA processing by increasing the affinity of DGCR8 to primary miRNA transcripts via deacetylation of critical lysine residues in the RNA-binding domains of DGCR8. This finding suggests that HDACs have two arms for gene silencing: transcriptional repression by promoter histone deacetylation and post-transcriptional inhibition by increasing miRNA abundance.
Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical School, Shimotsuke, Tochigi 329-0498, Japan.
Taeko
T
Wada
Jiro
J
Kikuchi
Yusuke
Y
Furukawa
D000107:Acetylation; D057809:HEK293 Cells; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D035683:MicroRNAs / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins
C474043:DGCR8 protein, human; D035683:MicroRNAs; D011506:Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1