Dynamic microRNA gene transcription and processing during T cell development

Francis F. Kirigin, Kenneth Lindstedt, Maclean Sellars, Maria Ciofani, Siao Li Low, Lachlan Jones, Fiona Bell, Florencia Pauli, Richard Bonneau, Richard M. Myers, Dan R. Littman, Mark M W Chong

Research output: Contribution to journalArticlepeer-review

Abstract

By disrupting microRNA (miRNA) biogenesis, we previously showed that this pathway is critical for the differentiation and function of T cells. Although various cloning studies have shown that many miRNAs are expressed during T cell development, and in a dynamic manner, it was unclear how comprehensive these earlier analyses were.We therefore decided to profile miRNA expression by next generation sequencing. Furthermore, we profiled miRNA expression starting from the hematopoietic stem cell. This analysis revealed that miRNA expression during T cell development is extremely dynamic, with 645 miRNAs sequenced, and the expression of some varying by as much as 3 orders of magnitude. Furthermore, changes in precursor processing led to altered mature miRNA sequences. We also analyzed the structures of the primary miRNA transcripts expressed in T cells and found that many were extremely long. The longest was pri-mir-29b-1/29a at ∼168 kb. All the long pri-miRNAs also displayed extensive splicing. Our findings indicate that miRNA expression during T cell development is both a highly dynamic and a highly regulated process.

Original languageEnglish (US)
Pages (from-to)3257-3267
Number of pages11
JournalJournal of Immunology
Volume188
Issue number7
DOIs
StatePublished - Apr 1 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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