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A high-throughput screen identifies the long non-coding RNA DRAIC as a regulator of autophagy


Autophagy is a conserved degradation process that occurs in all eukaryotic cells and its dysfunction has been associated with various diseases including cancer. While a number of large-scale attempts have recently identified new molecular players in autophagy regulation, including proteins and microRNAs, little is known regarding the function of long non-coding RNAs (lncRNAs) in the regulation of this process. To identify new long non-coding RNAs with functional implications in autophagy, we performed a high-throughput RNAi screen targeting more than 600 lncRNA transcripts and monitored their effects on autophagy in MCF-7 cells. We identified 63 lncRNAs that affected GFP-LC3B puncta numbers significantly. We validated the strongest hit, the lncRNA DRAIC previously shown to impact cell proliferation, and revealed a novel role for this lncRNA in the regulation of autophagic flux. Interestingly, we find DRAIC’s pro-proliferative effects to be autophagy-independent. This study serves as a valuable resource for researchers from both the lncRNA and autophagy fields as it advances the current understanding of autophagy regulation by non-coding RNAs.

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We thank Sudeep Sahadevan for analysis of RNA-seq data, Bettina Mentz for technical assistance, Kevin Ryan for providing pLenti-CRISPR NTC, ATG5, and ATG7 constructs [44], W Lee Kraus for providing PInducer20-DRAIC and -EV constructs [34]. Imke Tiessen was supported by the People Program (Marie Skłodowska-Curie Actions) of the European Union’s Seventh Framework Program FP7-PEOPLE-2013-ITN (Grant agreement no.: 607720). Work in the Lund laboratory was supported by the Danish Council for Independent Research (Sapere Aude program), the Novo Nordisk Foundation, the Lundbeck Foundation, the Danish Cancer Society and the EU COST Action Transautophagy (CA15138).

Author information

IT, ML, LBF, and AHL designed and interpreted the experiments. IT, LBF, and AHL wrote the manuscript. IT, MHA, and LBF performed experiments. CS and EJP assisted with screening and automated quantifications. HMG performed the GSEA analysis. SD provided the siRNA library and commented the manuscript.

Correspondence to Lisa B. Frankel or Anders H. Lund.

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