miRNA Nomenclature: A View Incorporating Genetic Origins, Biosynthetic Pathways, and Sequence Variants

Area of Science:

• Genomics
• Molecular Biology
• Bioinformatics

Background:

• High-throughput sequencing has uncovered extensive diversity in microRNAs (miRNAs) and related short noncoding RNAs.
• These include variations in genomic origins, biogenesis, and novel products like miRNA-offset RNAs (moRs).

Purpose of the Study:

• To review known alternative mature miRNA-like RNA fragments.
• To propose a revised definition of miRNAs that incorporates this observed diversity.
• To suggest extensions for miRNA nomenclature and a system for analyzing sequence variations (isomiRs).

Main Methods:

• Literature review of known miRNA variants and nomenclature guidelines.
• Analysis of high-throughput sequencing data to identify and characterize miRNA diversity.
• Development of a proposed framework for miRNA definition and nomenclature.

Main Results:

• Identification of diverse miRNA products beyond canonical miRNAs, including moRs.
• Demonstration of significant sequence variability (isomiRs) in mature miRNA populations.
• Proposal for an expanded miRNA definition and nomenclature system.

Conclusions:

• The current definition of miRNAs may be too narrow to encompass their full diversity.
• An updated nomenclature aligned with established gene conventions is needed.
• A systematic approach to analyzing isomiRs is crucial for comprehensive small RNA studies.