Context
Researchers at IISC Bangalore have identified a protein in yeast cells that dissolves RNA-protein complexes, also known as RNA granules.
Key-findings
- 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).
What is mRNA?
- 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.
What is an RNA granule?
- 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.
Treatment of disease
- 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.
Significance of the study
- 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.
