Parasital Non-Coding DNA Invoved in Sustaining Cellular Pluripotency

Parasital Non-Coding DNA Involved in Sustaining Cellular Pluripotency

Scientists from the RIKEN Center for Life Science Technologies in Japan, in collaboration with other research laboratories, have discovered that retrotransposons, viral elements incorporated into the human genome, may play a key role in the maintenance of pluripotency of cells.

In the current study, published in Nature Genetics, on embryonic stem (ES) cells and induced pluripotent stem (iPS) cells using four high-throughput analysis methods, the researchers found that thousands of transcripts in stem cells transcribed from retrotransposons, presumably to elicit nuclear functions. These transcripts were found to be expressed in stem cells, but not differentiated cells. Importantly, the work showed that several of these transcripts are involved in the maintenance of pluripotency, since degrading several of them using RNA interference caused iPS cells to lose their pluripotency and differentiate.

Evolution of retrotransposon domestication in the genome. This slide shows how long terminal repeats (LTRs), DNA sequences flanking retrotransposon segment where domesticated as regulatory sequences by mammalian genomes following a long evolutionary process.

Evolution of retrotransposon domestication in the genome. This slide shows how long terminal repeats (LTRs), DNA sequences flanking retrotransposon segment where domesticated as regulatory sequences by mammalian genomes following a long evolutionary process.

“Our work has just begun to unravel the scale of unexpected functions carried out by retrotransposons and their derived transcripts in stem cell biology. We were extremely surprised to learn from our data that what was once considered genetic ‘junk’, namely ancient retroviruses that were thought to just parasite the genome, are in reality symbiotic elements that work closely with other genes to maintain iPS and ES cells in their undifferentiated state. This is quite different from the image given by textbooks that these genomic elements are junk,” explains Dr. Piero Carninci, senior investigator of the study in a press release.

This research study was funded by a Japan Society for Promotion of Science (JSPS) grant for Next Generation World-Leading Researchers. In addition, the first author of the research paper, Swiss postdoctoral researcher Dr. Alexandre Fort, received SNSF post-doc fellowships funding.

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