Lineage and species-specific long noncoding RNAs during erythro-megakaryocytic development

Vikram R. Paralkar, Tejaswini Mishra, Jing Luan, Yu Yao, Andrew V. Kossenkov, Stacie M. Anderson, Margaret Dunagin, Maxim Pimkin, Meghneel Gore, Diana Sun, Neeraja Konuthula, Arjun Raj, Xiuli An, Narla Mohandas, David M. Bodine, Ross C. Hardison, Mitchell J. Weiss

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

Mammals express thousands of long noncoding (lnc) RNAs, a few of which are known to function in tissue development. However, the entire repertoire of lncRNAs in most tissues and species is not defined. Indeed, most lncRNAs are not conserved, raising questions about function. We used RNA sequencing to identify 1109 polyadenylated lncRNAs expressed in erythroblasts, megakaryocytes, and megakaryocyte-erythroid precursors of mice, and 594 in erythroblasts of humans. More than half of these lncRNAs were unannotated, emphasizing the opportunity for new discovery through studies of specialized cell types. Analysis of the mouse erythro-megakaryocytic polyadenylated lncRNA transcriptome indicates that ∼75% arise from promoters and 25% from enhancers, many of which are regulated by key transcription factors including GATA1 and TAL1. Erythroid lncRNA expression is largely conserved among 8 different mouse strains, yet only 15% of mouse lncRNAs are expressed in humans and vice versa, reflecting dramatic species-specificity. RNA interference assays of 21 abundant erythroid-specific murine lncRNAs in primary mouse erythroid precursors identified 7 whose knockdown inhibited terminal erythroid maturation. At least 6 of these 7 functional lncRNAs have no detectable expression in human erythroblasts, suggesting that lack of conservation between mammalian species does not predict lack of function.

Original languageEnglish (US)
Pages (from-to)1927-1937
Number of pages11
JournalBlood
Volume123
Issue number12
DOIs
StatePublished - Mar 20 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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