Studies in traditional genetics have revealed the molecular causes of many genetic diseases and provided direct clues for their prevention, diagnosis and treatments, as well as for various disorders with genetic background. However, the genetic profiles of most human diseases could not be fully explained with the canonical laws of genetics. Paramutation is one of non-Mendelian inheritance phenomenon, which was found in maize first in 1950s. The absence of alteration in nucleotide sequences in the gene-coding alleles suggested that paramutations might involve epigenetic mechanisms to transmit heritable changes in gene expression and determination of phenotypes. Recently, a novel epigenetic mechanism has been found in paramutation researches, emphasized the importance of DNA methyltransferase II mediated RNA (primarily non-coding RNAs) methylation in the occurrence and maintenance of paramutations. Researches on paramutations and their epigenetic mechnisms will not only expand our understanding in the genetic principles of life, but also help to develop new ideas for bioengineer and disease treatments. The present article reviewed the research highlights on molecular mechanisms of paramutation and discussed the prospects in disease study and therapy.
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