RNA granules to treat neurodegenerative disorders

[GS Paper – Biotechnology, Medicines]

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

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.

About RNA granules?

• 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.

Why are they unique?

• 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.

Functions of RNA granules

• 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.

Recent Studies on RNA Granules

• 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 types also present in the cytoplasm.

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.

About Neurological Disorders

• Neurological disorders are diseases of the central and peripheral nervous system. In other words, the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscles.

• Non-Communicable Neurological Disorders: Stroke, Headache disorders, Epilepsy, Cerebral palsy, Alzheimer’s disease and other dementias, Brain and central nervous system cancer, Parkinson’s disease, Multiple sclerosis, Motor neuron diseases, and other neurological disorders.

• Neurological disorders contribute 10% of the total disease burden in India. There is a growing burden of non-communicable neurological disorders in the country, which is mainly attributable to the aging of the population.

• The contribution of non-communicable neurological disorders to total DALYs (disability adjusted life-years) in India doubled from 4% in 1990 to 8·2% in 2019, and the contribution of injury-related neurological disorders increased from 0·2% to 0·6%.

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