TY - JOUR
T1 - Circular RNAs exhibit limited evidence for translation, or translation regulation of the mRNA counterpart in terminal hematopoiesis
AU - Nicolet, Benoit P.
AU - Jansen, Sjoert B. G.
AU - Heideveld, Esther
AU - Ouwehand, Willem H.
AU - van den Akker, Emile
AU - von Lindern, Marieke
AU - Wolkers, Monika C.
N1 - Funding Information: This research was supported by the European Research Council (ERC, consolidator grant), by the Dutch Science Foundation (Apasia grant), and by Oncode (all to M.C.W.). We also thank S. Heshusius for helpful discussions, and M. Hansen, P.J. van Alphen, and M. van den Biggelaar for critical reading of the manuscript. Publisher Copyright: © 2022 Cold Spring Harbor Laboratory Press. All rights reserved.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - 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.
AB - 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.
KW - CircRNA
KW - Megakaryocytes
KW - Platelets
KW - Red blood cells
KW - Translation
KW - Translation regulation
UR - http://www.scopus.com/inward/record.url?scp=85123813174&partnerID=8YFLogxK
U2 - https://doi.org/10.1261/rna.078754.121
DO - https://doi.org/10.1261/rna.078754.121
M3 - Article
C2 - 34732567
SN - 1355-8382
VL - 28
SP - 194
EP - 209
JO - RNA (New York, N.Y.)
JF - RNA (New York, N.Y.)
IS - 2
ER -