The vast little library inside your cells

Certain non-codingRNAs organize DNA and the associated cellular machinery. Each region is shown in a different jellybean-shape. Credit: Courtesy Of Inna Marie Strazhnik
Your genes are the instruction manuals for your genome. The human genome is a huge library that contains over 20,000 pages. There are genes that contain information about how to make a brain cell, skin cell, or white blood cell. Some genes even contain information about how to regulate the genome, such as books explaining how to set up a library. In other words, the ability of a cell to control gene expressionis what gives rise to different cell types (e.g. muscle cells or brain cells).

A library must be easily searchable in order to make it useful. All books on world history might be found on one shelf while cookbooks could be found in a different section. A cellular nucleus contains over six feet worth of genetic material. This is 50 times smaller than a human hair's width. How does the "library" within the nucleus get organized? How does the cell machinery locate the correct genes amongst the 20,000?

Mitchell Guttman's laboratory has published a new paper that uses a powerful tool to see inside the cells of genetic material (DNA, RNA), in order to answer these questions.

Sofia Quinodoz, a former Guttman lab graduate student and now a Hanna Gray postdoctoral Fellow at Princeton University, led the team. They discovered that non-codingRNA molecules are responsible for creating "compartments" in the nucleus as well as shepherding key molecules into specific regions of the genome. Non-coding RNA molecules are those that don't encode for proteins and have a variety of functions that remain largely unexplored by biologists. Non-coding RNA molecules are like libraries. They organize different types of genes and the machinery they interact with.

Understanding the spatial organization of genetic material is crucial to understanding how it works. Many diseases are characterized by dysfunction in the nucleus, such as cancer and neurodegenerative disorders.

This research was possible thanks to RD-SPRITE, a powerful tool created in the Guttman lab that allows detailed views of RNA's world. It is RNA and DNA Split-Pool Recognition Of Interactions by Tag Extension. RD-SPRITE basically works by tagging DNA and RNA molecules with tiny unique barcodes based upon their location. Analyzing the barcodes will reveal which molecules are at which position within the cell.

"This tool is something that I have longed for since I was a graduate student. Guttman says it's amazing that Sofia was able make this happen. It changes the way we see the RNA world. It's like a microscope that allows you to see things you couldn't before. The discovery of RNA and organizational structure is just the beginning of what we can find in these data.

The team will use RD-SPRITE in order to compare the nucleus' spatial organization between healthy and disease cells. This will allow them to better understand how gene expression may be affected by disease.

The paper is titled "RNA promotes formation of spatial compartments within the nucleus."

Continue reading The cartography for the nucleus

More information: Sofia A. Quinodoz and colleagues, RNA promotes formation of spatial compartments within the nucleus, Cell (2021). Information from the Journal: Cell Sofia A. Quinodoz and colleagues, RNA promotes formation of spatial compartments within the nucleus (2021). DOI: 10.1016/j.cell.2021.10.014