Dicer and Hsp104 function in a negative feedback loop to confer robustness to environmental stress

Area of Science:

• Molecular Biology
• Epigenetics
• Yeast Genetics

Background:

• Environmental cues can induce epigenetic changes, leading to phenotypic variation.
• The precise mechanisms by which temperature influences epigenetic alterations are not fully understood.
• Uncontrolled epigenetic plasticity can be detrimental.

Purpose of the Study:

• To investigate how environmental factors, specifically temperature, trigger epigenetic alterations.
• To identify the molecular players involved in buffering environmentally induced epigenetic variation.
• To understand the role of feedback regulation in epigenetic memory and protein homeostasis.

Main Methods:

• Utilized fission yeast as a model organism.
• Investigated the roles of RNase Dicer and protein disaggregase Hsp104.
• Analyzed heterochromatin stability and prionogenic protein aggregation under thermal stress.

Main Results:

• Demonstrated a negative feedback loop involving Dicer and Hsp104 that buffers temperature-induced epigenetic variation.
• Observed Dicer accumulation in cytoplasmic inclusions and heterochromatin instability at elevated temperatures in the absence of Hsp104.
• Showed that loss of Dicer leads to toxic aggregation of an exogenous prionogenic protein.

Conclusions:

• Hsp104 and Dicer function as homeostatic controllers of epigenetic memory.
• These proteins buffer environmentally induced stochastic epigenetic variation.
• Dicer and Hsp104 prevent toxic aggregation of prionogenic proteins, maintaining cellular homeostasis.