The limits of human microRNA annotation have been met

Area of Science:

• Genomics
• Molecular Biology
• Bioinformatics

Background:

• The number of human microRNAs (miRNAs) is debated, with recent studies reporting thousands of novel miRNAs beyond curated databases like MirGeneDB and miRBase.
• The human RNA atlas recently identified numerous putative miRNAs, adding to the controversy.

Purpose of the Study:

• To address concerns regarding the prediction and validation strategies for novel microRNAs.
• To evaluate the validity of recently reported putative microRNAs.
• To assert the approximate completeness of the human miRNA repertoire.

Main Methods:

• Quantification of established microRNA biogenesis-derived features.
• Analysis of prediction and functional validation strategies used in recent miRNA discovery studies.
• Comparison of putative novel miRNAs against established biogenesis criteria.

Main Results:

• The majority of reported novel microRNAs lack key biogenesis-derived features, indicating they are likely false positives.
• The human microRNA gene count is estimated to be near complete, around 550 genes.
• Current prediction tools require curation to prevent the propagation of false predictions.

Conclusions:

• The human microRNA complement is largely established, with approximately 550 miRNA genes.
• Flawed prediction strategies lead to the identification of false-positive microRNAs.
• Accurate miRNA identification is crucial for guiding research in biomarker discovery and therapeutic target development.