First step in treating some neurodegenerative disorders

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Last Updated17/05/2022

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

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Messenger RNA (mRNA) is a single-stranded RNA (Ribo Nucleic 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.

Inside the cytoplasm of any cell there are 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.

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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.

Messenger RNAs are converted to proteins (building blocks of the cell) by the process of translation.
RNA granules determine messenger RNA (mRNA) fate by deciding when and how much protein would be produced from mRNA.
Protein synthesis is a multi-step and energy-expensive process.
Therefore, a common strategy used by cells when it encounters unfavorable conditions is to shut down protein production and conserve energy to deal with a stressful situation.
RNA granules help in the process of shutting down protein production.
Some RNA granule types (such as Processing bodies or P-bodies) not only regulate protein production but also accomplish degradation and elimination of the mRNAs, which in turn helps in reducing protein production.

Researchers concluded that low complexity sequences which normally promote granule formation, in this case promote the disintegration of RNA granules in yeast cells.
They observed that the identified protein Sbp1 is specific for dissolving P-bodies and not stress granules which are related RNA granule type also present in the cytoplasm.

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.

At the onset, the aim of this study was not to look for possible interventions for neurodegenerative disorders.
Instead, the study was driven by our quest for answering a simple but powerful fundamental question about how RNA granules fall apart.
An important and satisfying take-home message from this study is that asking and addressing fundamental questions in science is equally important as doing ‘applied’ research.

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