Can RNA be inherited?

Mendel’s 1860s pioneering studies of pea plant crosses and breeding is a symbol of the foundation of modern inheritance mechanisms. As we know, DNA is the main carrier of genetic information from one generation to the next. However, RNAs can also be inherited and RNA methyltransferases can be important for the transmission and expression of modified phenotypes. Here we discuss possible mechanisms of RNA mediated inheritance and the role of these mechanisms for human health and disease.

Some of the best-known epigenetic mechanisms include chemical modifications of DNA and histone proteins and regulate the expression of genetic information by rendering the respective regions more or less accessible to the transcriptional machinery. DNA methylation patterns are erased in primordial germ cells and preimplantation embryos and then become re-established during the later stages of embryogenesis.

Several studies have shown that a complex and diverse set of RNAs is present in germ cells of both sexes, as well as in early embryos, and that miRNAs can be inherited, thus providing a possible mechanism for the transgenerational inheritance of altered phenotypes. DNMT2, which is highly expressed in mouse and human testes and ovaries, does not methylate DNA, but rather shows a pronounced substrate specificity towards a highly defined set of tRNAs.

RNA-mediated inheritance could provide a mechanism that allows a rapid adaptation to changing environmental conditions without affecting the genetic makeup of an organism.

One of the largest problems in the treatment of breast cancer is the development of multidrug resistance (MDR), where tumor cells possess or acquire the ability to circumvent the killing action of a variety of structurally unrelated chemotherapy drugs. The MDR mechanisms involve increased drug efflux from tumor cells due to induction of ATP-binding cassette (ABC) drug transporters. Higher expression of the ABCB1 drug transporter is often observed in drug-resistant tumor cells, although the precise mechanism remains unclear.

Recently epigenetic alterations including changes in methylation of CpG islands within gene promoters have emerged as a prominent mechanism for regulation of gene expression. CpG island methylation may repress transcription via the downstream promoter, while histone acetylation may play an important role in upstream promoter activation.

Through bisulfite sequencing experiments we found that the ABCB1 downstream promoter became increasingly methylated following the acquisition of drug resistance. This hypermethylation in turn correlated with increased ABCB1 gene amplification, a switch from usage of the ABCB1 downstream promoter to the upstream promoter, increased ABCB1 expression, and increased drug resistance. The cytotoxic activity of docetaxel is exerted by promoting and stabilising microtubule assembly, while preventing physiological microtubule disassembly in the absence of GTP.

This study is the first to examine broad-scale changes in ABCB1 gene methylation associated with the acquisition of docetaxel resistance and the first report of ABCB1 transcription exclusively via the upstream promoter.

Numerologist Warda is hooked on OG-L002 fishing, collecting. And lastly her encouragement comes from socializing along with her companions.