The RNA of the "fossil" retrovirus is a reliable marker of pluripotency
Retrovirus in the human genome is active in pluripotent stem cells
LifeSciencesToday based on ScienceDaily: Retrovirus in the Human Genome Is Active in Pluripotent Stem CellsAccording to a new study published by scientists at the University of Massachusetts Medical School (University of Massachusetts Medical School)
In the journal Retrovirology (Santoni et al., HERV-H RNA is abundant in human embryonic stem cells and a precise marker for pluripotency), the HERV-H retrovirus, introduced into the human genome millions of years ago, may play an important role in pluripotent stem cells. Pluripotent stem cells can give rise to cells of all types of tissues, including blood, brain and heart cells. This discovery, which explains how cells maintain a state of pluripotency and the ability to differentiate, may be of great importance for the development of treatments for a number of diseases.
"A group of endogenous retroviruses called HERV-H are extremely common in human embryonic stem cells," says Jeremy Luban, MD, professor of molecular medicine, lead author of an article about the study. "In fact, HERV-H is one of the most frequently expressed genes of pluripotent stem cells, and it is not found in other types of cells."
In their article, Professor Luban and his colleagues cite data that HERV-H RNA sequences make up as much as 2 percent of all pluripotent stem cell RNAs. The HERV-H RNA sequence is controlled by the same factors that are used to reprogram skin cells into induced pluripotent stem cells – a discovery awarded the 2012 Nobel Prize in Physiology or Medicine.
"In other words, HERV-H is a new marker of human cell pluripotency, which can help in reprogramming cells into induced pluripotent and change today's technologies," says Dr. Luban.
When cells are infected with a retrovirus, its genes are introduced into the chromosomal DNA of the host cell. As a result, the host cell considers the viral genome to be part of its DNA and begins to synthesize proteins necessary for assembling new copies of the virus. And since the retrovirus is now part of the genome of the host cell, when the cell divides, the virus is inherited by all daughter cells.
It is believed that in rare cases retroviruses can infect human sperm or eggs. If this happens and the infected embryo survives, the retrovirus can become a permanent part of the human genome and be transmitted from generation to generation. Scientists have estimated that as much as 8 percent of the human genome may consist of extinct retroviruses left over from an infection that occurred millions of years ago. However, these sequences of fossil retroviruses were thought to have no noticeable functional significance.
"The human genome is filled with retroviral DNA, which was considered nothing more than fossilized garbage," says Professor Luban. "Increasingly, there is evidence that these sequences may not be garbage. After all, they can play an important role in gene expression."
An expert in the field of HIV and other retroviruses, Professor Luban is trying to understand whether there is a logical explanation for exactly where retroviruses are embedded in the vast human genome. Knowing where retroviruses can attack chromosomal DNA may lead to the development of drugs that protect against infections, more effective gene therapy methods, or new biomarkers that can predict where a retrovirus can embed itself in the genome.
Scientists have established that the HERV-H sequence in the human genome is active.
"These sequences do not encode proteins, because they have been greatly destroyed over millions of years, but they encode long non–coding RNAs," explains Dr. Luban.
In particular, the HERV-H sequence encodes a large amount of RNA in human embryonic stem cells – and only in stem cells. In general, more than 1,000 HERV-H retroviral sequences are scattered throughout the human genome. In addition, Luban's lab found high levels of HERV-H encoded RNAs in some induced pluripotent stem cells. Other iPS cells, possibly from lines that were not fully reprogrammed into a pluripotent state, had lower levels of HERV-H RNA – further evidence that HERV-H may be a reliable marker of pluripotency.
Interestingly, HERV-H genes expressed in human pluripotent stem cells can only be found in human and chimpanzee genomes, indicating that HERV-H infected a human ancestor relatively recently.
"Once upon a time, HERV-H was an invader of our genome and may have caused diseases such as AIDS or cancer," says Dr. Luban. "Now, it seems, a kind of truce has been reached. Moreover, one day this ancient invader may be used by doctors to treat a wide range of diseases using stem cells."
In the near future, Professor Luban and his colleagues are going to investigate the specific mechanisms by which HERV-H promotes cell pluripotency.
Portal "Eternal youth" http://vechnayamolodost.ru25.01.2013