Circular RNA enrichment in platelets is a signature of transcriptome degradation

Alhasan, A. A. et al. (2016) Circular RNA enrichment in platelets is a signature of transcriptome degradation. Blood, 127(9), e1-e11. (doi: 10.1182/blood-2015-06-649434) (PMID:26660425)

Abstract

In platelets, splicing and translation occur in the absence of a nucleus. However, the integrity and stability of mRNAs derived from megakaryocyte progenitor cells remain poorly quantified on a transcriptome-wide level. As circular RNAs (circRNAs) are resistant to degradation by exonucleases, their abundance relative to linear RNAs can be used as a surrogate marker for mRNA stability in the absence of transcription. Here we show that circRNAs are enriched in human platelets 17-188 fold relative to nucleated tissues, and 14-26 fold relative to samples digested with RNAse R to selectively remove linear RNA. We compare RNAseq read depths inside and outside circRNAs to provide in silico evidence of transcript circularity, show that exons within circRNAs are enriched on average 12.7X in platelets relative to nucleated tissues, and identify 3162 genes significantly enriched for circRNAs, including some where all RNAseq reads appear to be derived from circular molecules. We also confirm that this is a feature of other anucleate cells through transcriptome sequencing of mature erythrocytes, demonstrate that circRNAs are not enriched in cultured megakaryocytes, and that linear RNAs decay more rapidly than circRNAs in platelet preparations. Collectively, these results suggest that circulating platelets have lost over 90% of their progenitor mRNAs, and that translation in platelets occurs against the backdrop of a highly degraded transcriptome. Finally, we find that transcripts previously classified as products of reverse transcriptase template switching are both enriched in platelets and resistant to decay, countering the recent suggestion that up to 50% of rearranged RNAs are artifacts.

• Item Type: Articles
• Additional Information: The financial support from the Leverhulme Trust (grant RPG-2012-795 to MSJ, MSK and DE), BBSRC (studentship BB/J014516/1 to OI), and the Wellcome Trust (grants WT089225MA and WT089225/Z/09/Z to DE) is gratefully acknowledged.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mountford, Dr Joanne and Marenah, Dr Lamin
• Authors: Alhasan, A. A., Izuogu, O. G., Al-Balool, H. H., Steyn, J. S., Evans, A., Colzani, M., Ghevaert, C., Mountford, J. C., Marenah, L., Elliott, D. J., Santibanez-Koref, M., and Jackson, M. S.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Life Sciences
• Journal Name: Blood
• Publisher: American Society of Hematology
• ISSN: 0006-4971
• ISSN (Online): 1528-0020
• Copyright Holders: Copyright © 2016 The American Society of Hematology
• First Published: First published in Blood 127(9):e1-e11
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher