Journal article
DROSHA but not DICER is required for human haematopoietic stem cell function
K Gu, C Walpole, S Gooneratne, X Liu, OL Haigh, KJ Radford, MMW Chong
Clinical and Translational Immunology | Published : 2022
DOI: 10.1002/cti2.1361
Abstract
Objectives: DROSHA and DICER have central roles in the biogenesis of microRNAs (miRNAs). However, we previously showed that in the murine system, DROSHA has an alternate function where it directly recognises and cleaves protein-coding messenger (m)RNAs and this is critical for safeguarding the pluripotency of haematopoietic stem cells (HSCs). Maintenance of murine HSC function is dependent on DROSHA-mediated cleavage of two mRNAs, Myl9 and Todr1. The goal of this study is to determine whether this pathway is conserved in human HSCs. Methods: DROSHA and DICER were knocked down in human cord blood CD34+ HSCs with short hairpin RNAs. The function of HSCs was analysed in vitro and in humanised m..
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Awarded by U.S. Department of Defense
Funding Acknowledgements
This work was supported by grants and fellowships from the National Health and Medical Research Council (1117154, 1122384 and 1122395 to MMWC), Diabetes Australia Research Trust (Y20G-CHOM to MMWC), US Department of Defense (W81XWH-19-1-0728 to MMWC), The Ann Helene Toakley Charitable Endowment (to MMWC) and the Mater Foundation (to KJR). St. Vincent's Institute of Medical Research is supported by the Victorian State Government Operational Infrastructure Support and the Independent Research Institutes Infrastructure Support Scheme of the National Health and Medical Research Council. The Translational Research Institute is supported by a grant from the Australian Government.