# gst: apropos of the structure of natural codes, a RNA folding knot (origami-style) dance

 << Every second, a myriad of shapeless strands of RNA fold, origami-style, into intricate structures inside living cells. Now, for the first time, researchers can watch a data-driven video of this folding as RNA molecules are made by the cellular machinery. >> 

<< as the RNA strand grows, it twists, forming knot-like structures. But as more RNA building blocks are added to the strand, the knots unravel, allowing the molecule’s structure to emerge. >> 

Ground-breaking films show RNA’s complex curves take shape. Experimental data and predictive algorithms combine to reveal the essential biomolecule’s shape-shifting.

Nature. Jan 19, 2021. 

https://www.nature.com/articles/d41586-021-00126-8

AA << model the folding of an RNA called SRP, an ancient RNA found in all kingdoms of life. The molecule is well-known for its signature hairpin shape. When watching the videos, the researchers discovered that the molecule ties itself into a knot and unties itself very quickly. Then it suddenly flips into the correct hairpin-like structure using an elegant folding pathway called toehold mediated strand displacement. >>

<< To the best of our knowledge, this has never been seen in nature, (..) We think the RNA has evolved to untie itself from knots because if knots persist, it can render the RNA nonfunctional. The structure is so essential to life that it had to evolve to find a way to get out of a knot. >> Julius Lucks. 

Amanda Morris. New Videos Show RNA as it's Never Been Seen. First-ever data-driven movies illuminate RNA's mysterious folding process.  McCormick School of Engineering. Jan 15, 2021.

https://www.mccormick.northwestern.edu/news/articles/2021/01/new-videos-show-rna-as-its-never-been-seen.html 

https://youtu.be/2XTi9LG9NnU

Angela M Yu, Paul M. Gasper, et al. Computationally reconstructing cotranscriptional RNA folding from experimental data reveals rearrangement of non-native folding intermediates. Molecular Cell. doi: 10.1016/ j.molcel.2020.12.017

Jan 15, 2021. 

https://www.cell.com/molecular-cell/fulltext/S1097-2765(20)30936-9

# gst: apropos how to manage misfolding (proteins)

<< Proteins are made up of chains of amino acids and during their formation they must fold to acquire an appropriate shape enabling them to perform their functions. However, when cells are subjected to stress or harm, such as high temperatures, some of the proteins may not fold properly. >>

<< There are three ways to solve the problem. The first option is to try to fix the folding in order to regain function, but this can be tricky because if stress conditions continue, the proteins continue unfolding. A second way is to destroy proteins that have not properly folded by way of machinery called proteasomes. But, in this study we reveal that the dominant route in yeast is a third option consisting of the formation of aggregates to protect misfolded proteins from degradation, >> Elena Hidalgo.

The strategy of cells to deal with the accumulation of misfolded proteins is identified. Universitat Pompeu Fabra. 

 Barcelona.  Feb 21, 2020.

https://m.phys.org/news/2020-02-strategy-cells-accumulation-misfolded-proteins.html

Margarita Cabrera, Susanna Boronat, et al. Chaperone-Facilitated Aggregation of Thermo-Sensitive Proteins Shields Them from Degradation during Heat Stress. Cell Reports. Vol 30, Issue 7, P2430-2443.E4. Feb 18, 2020. 

https://www.cell.com/cell-reports/fulltext/S2211-1247(20)30102-9