Hypoxia induces alterations in tRNA modifications involved in translational control

Area of Science:

• Molecular Biology
• Genomics
• Physiology

Background:

• High-altitude adaptation involves physiological and genetic changes.
• RNA modifications are crucial for organ function and sensitive to environmental factors.
• The role of RNA modifications in hypobaric hypoxia adaptation is not fully understood.

Purpose of the Study:

• To investigate the tissue-specific distribution of RNA modifications in mice under hypobaric hypoxia.
• To understand the molecular mechanisms underlying RNA modification changes during hypoxia exposure.

Main Methods:

• Utilized an LC-MS/MS platform to detect RNA modifications across mouse tissues.
• Analyzed RNA modifications in total RNA, tRNA fragments, and small non-coding RNAs (sncRNAs).
• Employed RNase digestion and in vitro transfection experiments to assess functional impacts.

Main Results:

• Identified tissue-specific patterns of multiple RNA modifications, linked to modifier gene expression.
• Observed significant alterations in RNA modification abundance across RNA groups in a hypoxia model.
• Hypoxia exposure destabilized tRNA and reduced nascent protein synthesis.

Conclusions:

• RNA modification abundance is tissue-specific and dynamically regulated by hypoxia.
• Dysregulated tRNA modifications under hypoxia impair cell proliferation and protein synthesis.
• The tRNA epitranscriptome plays a key role in the adaptive response to environmental hypoxia.