Differential processing of small RNAs during endoplasmic reticulum stress

Area of Science:

• Molecular Biology
• Cellular Biology
• Genetics

Background:

• Endoplasmic reticulum (ER) stress is induced by misfolded protein accumulation, triggering cellular responses.
• Small RNAs, including microRNAs (miRNAs), are known regulators of gene expression during stress.
• The precise role and processing of small RNAs in ER stress response remain incompletely understood.

Purpose of the Study:

• To investigate changes in small RNA expression and processing in Jurkat T-cells under ER stress.
• To identify specific small RNA molecules and processing alterations involved in the ER stress response.

Main Methods:

• Induction of ER stress in Jurkat T-cells.
• Analysis of small RNA composition and expression profiles.
• Characterization of miRNA isoforms and tRNA-derived fragments (tiRNAs).

Main Results:

• ER stress led to a depletion of miRNAs, with altered 3' end modifications (decreased adenylation/cytodination, increased 3' uridination).
• A specific subset of microRNAs (miRNAs) showed differential expression.
• A significant induction of 32-nt tRNA fragments (tiRNAs), phased with tRNA ends, was observed, linked to Angiogenin RNase.

Conclusions:

• Global perturbations in miRNA and tiRNA expression and processing are key features of the small RNA transcriptome during ER stress.
• Modulation of small RNA processing represents a significant layer in the complex cellular response to ER stress.
• These findings highlight novel regulatory mechanisms involving small RNAs in cellular homeostasis maintenance under stress.