Complexity of microRNA function and the role of isomiRs in lipid homeostasis

Kasey C Vickers, Praveen Sethupathy, Jeanette Baran-Gale, Alan T Remaley

Research output: Contribution to journalLiterature reviewpeer-review

Abstract

MicroRNAs (miRNAs) are key posttranscriptional regulators of biological pathways that govern lipid metabolic phenotypes. Recent advances in high-throughput small RNA sequencing technology have revealed the complex and dynamic repertoire of miRNAs. Specifically, it has been demonstrated that a single genomic locus can give rise to multiple, functionally distinct miRNA isoforms (isomiR). There are several mechanisms by which isomiRs can be generated, including processing heterogeneity and posttranscriptional modifications, such as RNA editing, exonuclease-mediated nucleotide trimming, and/or nontemplated nucleotide addition (NTA). NTAs are dominant at the 3'-end of a miRNA, are most commonly uridylation or adenlyation events, and are catalyzed by one or more of several nucleotidyl transferase enzymes. 3' NTAs can affect miRNA stability and/or activity and are physiologically regulated, whereas modifications to the 5'-ends of miRNAs likely alter miRNA targeting activity. Recent evidence also suggests that the biogenesis of specific miRNAs, or small RNAs that act as miRNAs, can occur through unconventional mechanisms that circumvent key canonical miRNA processing steps. The unveiling of miRNA diversity has significantly added to our view of the complexity of miRNA function. In this review we present the current understanding of the biological relevance of isomiRs and their potential role in regulating lipid metabolism.

Original languageEnglish
Pages (from-to)1182-91
Number of pages10
JournalJournal of lipid research
Volume54
Issue number5
DOIs
Publication statusPublished - May 2013

Keywords

  • Gene Expression Regulation
  • Genetic Variation
  • Homeostasis
  • Humans
  • Lipid Metabolism
  • Liver
  • MicroRNAs

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