Circular RNAs exhibit limited evidence for translation, or translation regulation of the mRNA counterpart in terminal hematopoiesis

Benoit P. Nicolet, Sjoert B. G. Jansen, Esther Heideveld, Willem H. Ouwehand, Emile van den Akker, Marieke von Lindern, Monika C. Wolkers

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)

Abstract

Each day, about 1012 erythrocytes and platelets are released into the bloodstream. This substantial output from hematopoietic stem cells is tightly regulated by transcriptional and epigenetic factors. Whether and how circular RNAs (circRNAs) contribute to the differentiation and/or identity of hematopoietic cells is to date not known. We recently reported that erythrocytes and platelets contain the highest levels and numbers of circRNAs among hematopoietic cells. Here, we provide the first detailed analysis of circRNA expression during erythroid and megakaryoid differentiation. CircRNA expression not only significantly increased upon enucleation, but also had limited overlap between progenitor cells and mature cells, suggesting that circRNA expression stems from regulated processes rather than resulting from mere accumulation. To study circRNA function in hematopoiesis, we first compared the expression levels of circRNAs with the translation efficiency of their mRNA counterpart. We found that only one out of 2531 (0.04%) circRNAs associated with mRNA-translation regulation. Furthermore, irrespective of thousands of identified putative open reading frames, deep ribosome-footprinting sequencing, and mass spectrometry analysis provided little evidence for translation of endogenously expressed circRNAs. In conclusion, circRNAs alter their expression profile during terminal hematopoietic differentiation, yet their contribution to regulate cellular processes remains enigmatic.
Original languageEnglish
Pages (from-to)194-209
Number of pages16
JournalRNA (New York, N.Y.)
Volume28
Issue number2
DOIs
Publication statusPublished - 1 Feb 2022

Keywords

  • CircRNA
  • Megakaryocytes
  • Platelets
  • Red blood cells
  • Translation
  • Translation regulation

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