Regulation of MicroRNA expression and abundance during lymphopoiesis

Stefan Kuchen, Wolfgang Resch, Arito Yamane, Nan Kuo, Zhiyu Li, Tirtha Chakraborty, Lai Wei, Arian Laurence, Tomoharu Yasuda, Siying Peng, Jane Hu-Li, Kristina Lu, Wendy Dubois, Yoshiaki Kitamura, Nicolas Charles, Hong wei Sun, Stefan Muljo, Pamela L. Schwartzberg, William E. Paul, John O'SheaKlaus Rajewsky, Rafael Casellas

Research output: Contribution to journalArticlepeer-review

286 Citations (Scopus)

Abstract

Although the cellular concentration of miRNAs is critical to their function, how miRNA expression and abundance are regulated during ontogeny is unclear. We applied miRNA-, mRNA-, and ChIP-Seq to characterize the microRNome during lymphopoiesis within the context of the transcriptome and epigenome. We show that lymphocyte-specific miRNAs are either tightly controlled by polycomb group-mediated H3K27me3 or maintained in a semi-activated epigenetic state prior to full expression. Because of miRNA biogenesis, the cellular concentration of mature miRNAs does not typically reflect transcriptional changes. However, we uncover a subset of miRNAs for which abundance is dictated by miRNA gene expression. We confirm that concentration of 5p and 3p miRNA strands depends largely on free energy properties of miRNA duplexes. Unexpectedly, we also find that miRNA strand accumulation can be developmentally regulated. Our data provide a comprehensive map of immunity's microRNome and reveal the underlying epigenetic and transcriptional forces that shape miRNA homeostasis.

Original languageEnglish
Pages (from-to)828-839
Number of pages12
JournalImmunity
Volume32
Issue number6
DOIs
Publication statusPublished - Jun 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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