RNA modulation of the human DNA methyltransferase 3A.
DNA methyltransferase 3A (DNMT3A) is one of two human de novo DNA methyltransferases essential for transcription regulation during cellular development and differentiation. There is increasing evidence that RNA plays a role in directing DNA methylation to specific genomic locations within mammalian cells. Here, we describe two modes of RNA regulation of DNMT3A in vitro. We show a single-stranded RNA molecule that is antisense to the E-cadherin promoter binds tightly to the catalytic domain in a structurally dependent fashion causing potent inhibition of DNMT3A activity. Two other RNA molecules bind DNMT3A at an allosteric site outside the catalytic domain, causing no change in catalysis. Our observation of the potent and specific in vitro modulation of DNMT3A activity by RNA supports in vivo data that RNA interacts with DNMT3A to regulate transcription.
Interdepartmental Program in Biomolecular Science and Engineering, University of California, Santa Barbara, CA 93106-9510, USA.
Celeste
C
Holz-Schietinger
Norbert O
NO
Reich
D015820:Cadherins / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D000090205:DNA Methyltransferase 3A; D006801:Humans; D009690:Nucleic Acid Conformation; D016372:RNA, Antisense / Q000737:chemistry / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism
D015820:Cadherins; C000717967:DNMT3A protein, human; D016372:RNA, Antisense; D034741:RNA, Small Interfering; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A