It is known that viruses use the genetic machinery of human cells that invade to make copies of themselves. As part of the process, viruses leave the remains in all the genetic material (genomes) of humans. Insertions similar to virus, called “transpononable elements”, are fragments of genetic material even simpler than viruses that also use host cell machinery to replicate.
Almost all these inserted elements have been silenced by the defense mechanisms of our cells over time, but some, nicknamed “skipping genes”, can still move around the human genome such as viruses. Only one, called Long Inclined Nuclear Element 1 (Line-1), can still move on your own.
As a type of element that behaves like Retrovirus HIV, the “Retrotransosposón” line is first copied into a RNA molecule, the genetic material that is associated with DNA, and then the copy of the RNA line-1 converts into DNA in a new place in the genome. In this way, retrotransposons add code to the human genome every time they move, which explains why 500,000 line repetitions now represent an “amazing” 20 percent of the human genome. These repetitions drive the evolution of the genome, but can also cause neurological diseases, cancer and aging when line 1 randomly jumps to essential genes, or triggers an immune response such as a virus to cause inflammation.
However, to copy itself, line 1 must enter the core of each cell, the internal barrier that houses the DNA. Now a new study, published online on May 2 in the magazine Scientific advancesIt reveals that the Line-1 joins the cell DNA during the brief periods when the nuclei open as the cells are continuously divided into two, creating replacements to keep the viable tissues as we age. The research team found that line 1 RNA take advantage of these moments, assembling in groups with one of the two proteins that CODIFIES, ORF1P, to closely maintain the DNA until the nucleus is reformed after cell division.
Directed by researchers from Nyu Langone Health and the Munich Genes Center in Ludwig-Maximilians-Universität (LMU) München in Germany, the work specifically revealed that line 1 can only join the DNA when orf1p, which can join the RNA, DNA, and in itself in linked copies called multimarse hundreds of hundreds of stockings. As more ORF1P molecules accumulate, they eventually involve the RNA of Line 1, which makes the most available union sites for the entire cluster join the DNA.
“Our study provides a crucial vision of how a genetic element that has created a large part of human DNA can successfully invade the nucleus to be copied, said Liam J. Holt, Phd., Associated professor in the department of biochemistry and molecular pharmacology, and the genetics of the Systems Institute, in Nyu Grossman School of Medicine of Medicine.” of future therapies to avoid the replication of line 1 “.
The work also suggests that the line-1 condensate acts as a delivery vehicle to bring its RNA to the proximity of the correct sequences (rich in the bases of Adenine and Timina DNA) in the DNA where the retrotransposon tends to insert, say the authors of the study. It is believed that in its condensate, it is believed that the Line-1 evade mechanisms that exclude large particles from the nucleus during mitosis as a cell defense against viruses.
“Line-1 condensates have a remarkable feature in which their ability to union to DNA arises only when the ratio of ORF1P copies with RNA is high enough in condensate,” added Dr. Holt. “Progressing, we will seek to see if other condensates suffer functional changes as relations between their components change.”
Together with Dr. Holt, the first study authors were the graduate student Farida Ettefa at the Nyu Grossman School of Medicine and its institutes for systems genetics; and Sarah Zernia of the Gene Munich Center in Ludwig-Maximilians-Universität (LMU) München in Germany. Also the authors of the study were Cas Koeman, Joëlle Deplazes-Lauber, Marvin Freitag and co-senior author Johannes Stigler of Ludwig-Maximilians-Universität München. The study was supported by the LMU-NYU Research Program.