Hypothesis of initiation of DNA methylation de novo and allelic exclusion by small RNAs

We have established that 5′-CG-3′ dinucleotide and 5′-CNG-3′ trinucleotide are found in published sequences of small interfering RNA and microRNA more often than they should be in random DNA sequences. This circumstance indicates the important biological role played by 5′-CG-3′ dinucleotides and 5′-CNG-3′ trinucleotides in small RNA sequences. We suggest that small RNAs containing these di- and trinucleotides participate in the creation of chromatin marks of epigenetic information through a highly specific search for repressible DNA sequences and through the initiation of the methylation de novo of 5′-CG-3′ and 5′-CNG-3′ sites in DNA fragments appearing to be bound complementary to small RNAs. Several genes can be inactivated simultaneously if they contain the motif recognized by small RNA. Allelic exclusion appears, in our opinion, as a result of initiation by small RNAs of DNA methylation de novo of all but one of the alleles that exist in the cell. The predecessor of this small RNA is transcribed from the antiparallel allele chain. Alleles whose antiparallel chains are less actively read by RNA polymerase, which, as we suggest, in the process of transcribing, releases DNA from small RNA bound to it, are inactivated. However, the quantity of small RNA transcribed from only one allele is insufficient to overcome the level above which the repression process of this allele is initiated de novo.