Context

• Dive into the cytoplasm of any cell and one comes across structures made of messenger RNA (mRNA) and proteins known as RNA granules, in general. 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

• 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.

Protein synthesis

• 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 unfavourable conditions is to shut down protein production and conserve energy to deal with the 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.

RNA granules and neurodegenerative disorders

• 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 such as ewing sarcoma breakpoint region 1 (EWSR1) and fused in sarcoma (FUS) are RNA binding proteins that can reside in RNA granules.
• These above-mentioned proteins also contain low complexity sequences (repeats of amino acids) that are important for their movement into RNA granules.
• 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 type also present in the cytoplasm.
• EWSR1 protein aggregates have been implicated in diseases such as ALS and FTD.
• Further experiments indicated that Sbp1 protein was important for reducing these EWSR1 aggregates, indicating that what we learned using yeast is likely to be true in the context of humans. This study has highlighted the potential of amino acid repeats (RGG) as a therapeutic intervention.

Reference:

https://www.thehindu.com/todays-paper/tp-features/tp-sci-tech-and-agri/first-step-in-treating-some-neurodegenerative-disorders/article65415470.ece

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