Journal
CELL REPORTS
Volume 15, Issue 8, Pages 1795-1808Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2016.04.059
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Funding
- Burroughs Wellcome Fund
- NIH/National Institute of General Medical Sciences [R01-GM083300]
- National Research Foundation, Prime Minister's Office, Singapore under its NRF Fellowship Progremme [NRF2011NRF-NRFF001-042]
- NUS Faculty of Science [R-154-000-536-133]
- AcRF [R-154-000-562-112]
- Lee Hiok Kwee fund [R-154-000-582-651]
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In Drosophila, Dicer-1 binds Loquacious-PB (Loqs-PB) as its major co-factor. Previous analyses indicated that loqs mutants only partially impede miRNA processing, but the activity of minor isoforms or maternally deposited Loqs was not eliminated in these studies. We addressed this by generating a cell line from loqs-null embryos and found that only similar to 40% of miRNAs showed clear Loqs dependence. Genome-wide comparison of the hairpin structure and Loqs dependence suggested that Loqs substrates are influenced by base-pairing status at the dicing site. Artificial alteration of base-pairing stability at this position in model miRNA hairpins resulted in predicted changes in Loqs dependence, providing evidence for this hypothesis. Finally, we found that evolutionarily young miRNA genes tended to be Loqs dependent. We propose that Loqs may have roles in assisting the de novo emergence of miRNA genes by facilitating dicing of suboptimal hairpin substrates.
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