Image credit: lisichik, via Pixabay.
Scientists at Caltech may have sounded the final death knell for the “junk DNA” myth. If only Dan Graur had known this years ago, it might have saved a lot of wasted rhetoric. ENCODE, readers recall, found that 80 percent of the genome is transcribed, even if only a small part codes for proteins. The functions of those non-coding regions were only hinted at. Now, the windows are opening on organization so all-encompassing for all those non-coding RNA transcripts, it is truly mind-boggling what goes on in the nucleus of a cell.
Using a new survey tool they call RD-SPRITE, Caltech researchers, in cooperation with others at USC and UCLA, mapped the spatial organization of all the DNA and RNA in the nucleus. It was challenging, they admit, to explore the spatial roles of RNA transcripts that don’t produce proteins, because the nucleus is a dynamic place crowded with DNA, proteins, and numerous RNAs of unknown function. Let them explain in their paper in Cell1 what they found in the resulting maps:
These maps reveal higher-order RNA-chromatin structures associated with three major classes of nuclear function: RNA processing, heterochromatin assembly, and gene regulation. These data demonstrate that hundreds of ncRNAs form high-concentration territories throughout the nucleus, that specific RNAs are required to recruit various regulators into these territories, and that these RNAs can shape long-range DNA contacts, heterochromatin assembly, and gene expression. These results demonstrate a mechanism where RNAs form high-concentration territories, bind to diffusible regulators, and guide them into compartments to regulate essential nuclear functions. [Emphasis added.]
A new picture begins to emerge of hierarchical organization in the nucleus. No longer does it look like spaghetti in a basketball. On the contrary, there are territories and compartments throughout the interior. Caltech’s work adds to earlier knowledge of nuclear compartments:
- Nucleolus: contains transcribed ribosomal RNAs and associated processing molecules
- Speckles: contain pre-mRNAs and splicing components
- Transcriptional condensates: contain RNA polymerase II machines and factors
Now, additional hierarchical organization is being found in the nucleus. In the newly identified territories are found ncRNAs (noncoding RNAs, not destined for protein) — thousands of them — that are doing important jobs: guiding regulators into the right territories where “essential nuclear functions” need to take place.
Floor Plan
Functional importance does not require that these ncRNAs exit the nucleus to be translated into proteins. Architecture is a function, is it not? Building designers carefully consider the floor plan of a large office, so that individuals can have cubicles for effective concentration as well as small conference rooms, large conference rooms, and labs for teamwork. What a picture is emerging of a fully functioning genome. It’s like a high-tech business organized for optimum workflow.
This is the first global map of nuclear organization that includes DNA, RNA and protein. Caltech scientists have been investigating how these easily diffusible molecules become spatially organized. Earlier, their SPRITE method, first reported in 2018, enabled them to examine pairwise contacts on a small scale. Now, their newly improved RD-SPRITE’s wide-angle mapping capability brings the overall organization into focus.
We recently developed SPRITE, which utilizes split-and-pool barcoding to generate comprehensive and multi-way 3D maps of the nucleus across a wide range of distances (Quinodoz et al., 2018). …….
Source: https://evolutionnews.org/2021/12/caltech-finds-amazing-role-for-noncoding-dna/