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First step in treating some neurodegenerative disorders

  • Published
    16th May, 2022
Context

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

Background

Messenger RNA (mRNA):

  • mRNA fate decisions play a crucial role in regulating variety of cellular processes including development and differentiation, synaptic plasticity, ageing and diseases such as cancer, neurodegenerative disorders and cystic fibrosis.
  • The proteins associated with mRNA control its individual fate in the cytosol by promoting certain functional transitions and inhibiting others. 
  • 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.
  • Important feature of 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
  • 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 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.

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).
  • 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.
  • 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.

Messenger RNA (mRNA):

  • mRNA fate decisions play a crucial role in regulating variety of cellular processes including development and differentiation, synaptic plasticity, ageing and diseases such as cancer, neurodegenerative disorders and cystic fibrosis.
  • The proteins associated with mRNA control its individual fate in the cytosol by promoting certain functional transitions and inhibiting others. 
  • 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.
  • Important feature of 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
  • 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 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.

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).
  • 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.
  • 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.
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