Scientists discovered an unexpected gene in nematodes that challenged the theory of nuclear structure

Nucleolin has been linked
to neurodegenerative diseases and cancer in humans.
But the new findings challenge recent theories about the role that the internal structure of the nucleus may play in this disease, and provide a powerful new tool
for studying Nucleolin's function and how it contributes to disease.

"Nucleolin is a versatile protein that is present in many animals, plants, and fungi, but was previously thought to be absent in nematodes," Spaulding said
.
"It has also been linked to familial amyotrophic lateral sclerosis (ALS) and Alzheimer's disease, while global nucleolar dysfunction has been linked
to neurodegeneration.
"

Their identification of NUCL-1 establishes a new discovery platform
for nematodes as nucleolin neuronal function and associated neurodegenerative genetics.

Nucleolin is mainly found in nucleoli, which are factories
for the assembly of nucleosomes in the cell.
Unlike many other membrane-bound organelles within the cell, the nucleoli behave like a large droplet, also known as a condensate
.

Condensate is formed
by liquid-liquid phase separation.
Some imagine the formation of spots of varying densities inside lava lamps, but exactly how this is achieved in living cells is unclear
.

Surprisingly, disrupting phase separation had no effect on health and fertility

Because nematodes are particularly well-suited to intravital microscopy, which can provide a close-up look at endogenous proteins inside living animals, the discovery could change scientists' perception
of the characteristics of condensates, such as nucleoli.

Spaulding compares kernels to lollipops
.
"It's layered inside and out," she said
.
"Some proteins are localized in the innermost layer and some proteins are localized in the outermost layer
.
Each layer is thought to represent a step
in the biogenesis of ribosomes.
”

The biological significance of the condensate substructure is questionable.
Recent ideas suggest that the precise, hierarchical spatial organization of nucleoli is critical
for ribosome production.
But MDIBL scientists observed that when NUCL-1 was removed and the nucleoli structure inside germ cells was destroyed, the mutants could still develop normally and produce normal offspring
.

"We noticed that when we removed the area of the nucleoli, the nucleoli lost its beautiful substructure, but the nematodes were completely fine
," she said.
This was an accident, suggesting that this precise layered organization is not as important
for nucleolar function as we thought.
This may be important for understanding ALS, or Alzheimer's, where widespread phase separation disruption is thought to be the cause of the
disease.
”

"This will be something that really affects the field of phase separation because many of the conclusions drawn may not be correct
.
" These results should generate broad interest and will lead to new avenues
of research in areas such as phase separation, nucleolar structure and function, and nucleolar-related human diseases.
”

RG/RGG repeats in the C.
elegans homologs of Nucleolin and GAR1 contribute to sub-nucleolar phase separation