Ambros and colleagues discovered the first known microRNA (miRNA), a small single-stranded non-coding RNA molecule (containing about 22 nucleotides) found in plants, animals and some viruses, that functions in RNA silencing and post-transcriptional regulation of gene expression. The human genome may encode over 1900 miRNAs, although more recent analysis suggests that the number is closer to 2,300.

The first human disease associated with deregulation of miRNAs was chronic lymphocytic leukemia. In this disorder, the miRNAs work as both tumor suppressors and oncogenes.

In 2024 Victor Ambros shared the Nobel Prize in Physiology or Medicine Gary Ruvkun for "the discovery of microRNA and its role in post-transcriptional gene regulation."

Order of authorship in the original publication: Lee, Feinbaum, Ambros.