A mouse tissue atlas of small noncoding RNA.

Area of Science:

• Molecular Biology
• Genomics
• Biochemistry

Background:

• Small noncoding RNAs (ncRNAs) are crucial regulators of biological processes.
• Understanding the tissue-specific expression of ncRNAs is vital for deciphering their roles in health and disease.
• A comprehensive quantitative reference of small ncRNA expression is needed.

Purpose of the Study:

• To systematically profile and quantify the expression levels of five classes of small ncRNAs across 11 mouse tissues.
• To identify tissue-specific and sexually dimorphic small ncRNA expression patterns.
• To investigate the cell-type origins of brain-specific ncRNAs.

Main Methods:

• Deep sequencing of five small ncRNA classes (miRNA, snoRNA, snRNA, scaRNA, tRNA fragments) in 11 mouse tissues.
• Analysis of 14 biological replicates across both sexes.
• Integration with single-cell chromatin accessibility (scATAC-seq) data.

Main Results:

• Approximately 30% of small ncRNAs exhibit tissue-specific distribution, with some showing sexual dimorphism.
• MicroRNAs (miRNAs) can undergo "arm switching" between healthy tissues.
• Transfer RNA (tRNA) fragments are retained in a gene- and tissue-specific manner.
• The brain harbors the highest number of unique small ncRNA transcripts, including novel ones.
• Brain-specific ncRNAs were successfully linked to their cell types of origin using scATAC-seq data.

Conclusions:

• This study presents the most comprehensive characterization of small RNA expression in individual murine tissues to date.
• The identified ncRNA expression patterns offer a valuable resource for future research into ncRNA function in tissue homeostasis and disease pathogenesis.
• The findings highlight the complexity and specificity of small ncRNA regulation across different tissues and cell types.