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Long non-coding RNAs in B cell development and activation

Tiago F. Brazão, Jethro S. Johnson, Jennifer Müller, Andreas Heger, Chris P. Ponting and Victor L.J. Tybulewicz

Key points

  • 4516 long non-coding RNAs identified across multiple stages of B cell development and activation.

Abstract

Long noncoding RNAs (lncRNAs) are potentially important regulators of cell differentiation and development, but little is known about their roles in B-lymphocytes. Using RNA-seq and de novo transcript assembly, we identified 4516 lncRNAs expressed in 11 different stages of B cell development and activation. Most of these lncRNAs have not been previously detected, even in the closely related T cell lineage. Comparison with lncRNAs previously described in human B cells identified 185 mouse lncRNAs that have human orthologues. Using ChIP-seq we classified 20% of the lncRNAs as either enhancer-associated (eRNA) or promoter-associated (pRNA) RNAs. We identified 126 eRNAs whose expression closely correlated with the nearest coding gene, thereby indicating the likely location of numerous enhancers active in the B cell lineage. Furthermore, using this catalogue of newly discovered lncRNAs we show that PAX5, a transcription factor required to specify the B cell lineage, bound to and regulated the expression of 109 lncRNAs in pro-B and mature B cells and 184 lncRNAs in acute lymphoblastic leukemia.

  • Submitted November 16, 2015.
  • Accepted June 28, 2016.