Enhanced RNA quality control maintains long-term regenerative ability in planarians

Area of Science:

• Molecular Biology
• Regenerative Medicine
• Animal Model Studies

Background:

• Planarians exhibit remarkable regenerative capacity throughout adulthood, unlike most animals experiencing age-related decline.
• This regeneration is mediated by adult stem cells called neoblasts.
• Neoblasts express SMEDWI-1, a PIWI protein crucial for RNA regulation, with homologs in other long-lived and germ cells.

Purpose of the Study:

• To investigate the function of SMEDWI-1 in planarian neoblasts.
• To understand the molecular mechanisms underlying age-related decline in regeneration.
• To identify the downstream consequences of SMEDWI-1 depletion in planarians.

Main Methods:

• RNA interference (RNAi) to deplete SMEDWI-1 in planarians.
• Assessment of wound repair and regeneration capabilities.
• Analysis of secreted proteins and intracellular protein aggregation.
• Investigation of the signal recognition particle (SRP) assembly and function.

Main Results:

• SMEDWI-1 depletion leads to accumulation of non-coding and aberrant RNAs.
• Animals lacking SMEDWI-1 show impaired wound repair, regeneration, altered secreted proteins, and increased protein aggregation.
• These defects are linked to the misassembly of the signal recognition particle (SRP).
• Accumulated RNAs disrupt SRP function, compromising proteostasis.

Conclusions:

• SMEDWI-1 is essential for maintaining RNA homeostasis in planarian neoblasts.
• Proper RNA regulation by SMEDWI-1 is critical for preventing defects in protein secretion and proteostasis.
• Dysregulation of non-coding RNAs due to SMEDWI-1 loss progressively impairs organismal vigor and regenerative capacity.