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LINE dancing - a new and essential role for repetitive DNA in embryonic development

June 21, 2018

 

Two-cell mouse embryo stained for LINE1 RNA (magenta)

   
Two-cell mouse embryo stained for LINE1 RNA (magenta), which is expressed in the two cell nuclei. Credit Ramalho-Santos lab / UCSF  

Biologists have long known about segments of repeated sequences of DNA – together such elements comprise almost half of our genomes (and those of other species). Indeed, they’ve been a pain in the neck for those scientists tasked with determining the genome sequences of organisms – acting like white pieces of a jigsaw puzzle of a high arctic snow scene. These elements derive from the long-ago actions of “transposable elements” that can initially replicate themselves and hop around the genome but then lose this mobility and sit, scar-like, throughout chromosomes. A research team led by Dr. Miguel Ramalho-Santos has now uncovered an important and novel role for the most common of these repetitive elements, called LINE1, which accounts for a full 24% of the human genome. His group has found that this element is critical for very early mouse embryos to successfully compete their journey from two cells to four cells. Miguel’s group found that embryonic stem cells express unusually high levels of LINE1 RNA and when this production was interfered with in fertilized eggs, the embryos became stuck at the two-cell stage. They went on to discover that the LINE1 RNA binds to other key proteins in the nucleus of the embryos cells (specifically nucleolin and Kap1) and acts to switch the pattern of gene expression to allow further embryonic development.

This work was performed at UC San Francisco (a detailed description of the work by the UCSF public affair team can be found here: https://www.ucsf.edu/news/2018/06/410781/not-junk-jumping-gene-critical-early-embryo ). Dr. Ramalho-Santos was recently awarded a prestigious Canada 150 Chair and will be starting his new laboratory at the Lunenfeld-Tanenbaum Research Institute this July.
 

A LINE1-Nucleolin partnership regulates early development and ES cell identity
Michelle Percharde, Chih-Jen Lin, Yafei Yin, Juan Guan, Gabriel A. Peixoto, Aydan Bulut-Karslioglu, Steffen Biechele, Bo Huang, Xiaohua Shen and Miguel Ramalho-Santos. Cell. [https://www.cell.com/cell/fulltext/S0092-8674(18)30655-X]

 

 

 

 

 

 

 

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