Extracellular microRNA 3' end modification across diverse body fluids

Area of Science:

• Molecular Biology
• Bioinformatics
• Genomics

Background:

• MicroRNAs (miRNAs) are key regulators of gene expression.
• Extracellular miRNAs are present in biofluids, but their sequence variations are understudied.
• Previous analyses focused on overall miRNA expression, neglecting isoforms and modifications.

Purpose of the Study:

• To develop a bioinformatics tool (miNTA) for identifying miRNA 3' non-templated additions (NTAs).
• To analyze NTA profiles in a large cohort of extracellular RNA sequencing data.
• To explore the potential of NTAs as biomarkers and their functional implications.

Main Methods:

• Development of the miNTA bioinformatics tool for NTA identification.
• Analysis of 1047 extracellular RNA sequencing datasets from four biofluid types.
• Quantification and comparison of miRNA 3' uridylation and adenylation levels.

Main Results:

• Hundreds of miRNAs with 3' uridylation and adenylation were identified, with uridylation being more common.
• Significant levels of 3' uridylation (53%) and adenylation (22%) were observed in specific biofluids.
• 3' uridylation levels effectively distinguished biofluid types, outperforming overall miRNA expression.
• Extracellular uridylated miRNAs are linked to angiogenesis, apoptosis, and inflammation.

Conclusions:

• miRNA 3' NTA profiles provide robust, fluid-specific information.
• NTA analysis offers a novel avenue for biomarker discovery in biofluids.
• This study establishes a comprehensive landscape of miRNA NTAs, supporting future research.