RNA granules

Context

Researchers at IISC Bangalore have identified a protein in yeast cells that dissolves RNA-protein complexes, also known as RNA granules.

In recent years, a strong link has emerged between RNA granules and neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD).
A recent study has identified a protein (Sbp1) as a factor that dissolves the RNA granules (P-bodies).
The work also concluded that low complexity sequences (containing repeats of arginine (R) and glycine (G) amino acids — RGG) which normally promote granule formation, in this case promote the disintegration of RNA granules in yeast cells.
The identified protein Sbp1 is specific for dissolving P-bodies and not stress granules which are related RNA granule types also present in the cytoplasm.
This finding can be used to treat neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD).

Messenger RNA (mRNA) is a single-stranded RNA (RiboNucleic Acid) molecule that is complementary to one of the DNA strands of a gene.
The mRNA is an RNA version of the gene that leaves the cell nucleus and moves to the cytoplasm where proteins are made.
During protein synthesis, an organelle called a ribosome moves along the mRNA, reads its base sequence, and uses the genetic code to translate each three-base triplet, or codon, into its corresponding amino acid.

In the cytoplasm of any cell one comes across structures made of messenger RNA (mRNA) and proteins known as RNA granules.
Unlike other structures in the cell (such as mitochondria), the RNA granules are not covered and confined by a membrane.
This makes them highly dynamic in nature, thereby allowing them to constantly exchange components with the surrounding.
RNA granules are present in the cytoplasm at low numbers under normal conditions but increase in number and size under stressful conditions including diseases.
A defining feature which does not change from one organism to another (conserved) of the RNA granule protein components is the presence of stretches containing repeats of certain amino acids.
Such stretches are referred to as low complexity regions.

Repeats of arginine (R), glycine (G) and glycine (G) — known as RGG — are an example of low complexity sequence.

In recent years, a strong link has emerged between RNA granules and neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD).
The proteins implicated in these diseases are RNA binding proteins that can reside in RNA granules.
These proteins also contain low complexity sequences (repeats of amino acids) that are important for their movement into RNA granules.
In fact, these proteins are deposited as insoluble granules/aggregates in the neurons of ALS and FTD patients which are believed to contribute to the pathophysiology of these diseases.
Finding ways of solubilizing these aggregates could provide a breakthrough in treating these diseases.

This study has highlighted the potential of amino acid repeats (RGG) as a therapeutic intervention.
The study may help analyze the effect of repeat sequences in genetically engineered mice that accumulate insoluble pathological aggregates in brain cells.
This could possibly help in treating neurodegenerative disorders such as Alzheimer’s disease.