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

TY - JOUR

T1 - A high-throughput screen identifies the long non-coding RNA DRAIC as a regulator of autophagy

AU - Tiessen, Imke

AU - Abildgaard, Marie H

AU - Lubas, Michal

AU - Gylling, Helene M

AU - Steinhauer, Cornelia

AU - Pietras, Elin J

AU - Diederichs, Sven

AU - Frankel, Lisa B

AU - Lund, Anders H

PY - 2019/6/27

Y1 - 2019/6/27

N2 - 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.

AB - 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.

U2 - 10.1038/s41388-019-0783-9

DO - 10.1038/s41388-019-0783-9

M3 - Journal article

C2 - 30872794

SN - 0950-9232

VL - 38

SP - 5127

EP - 5141

JO - Oncogene

JF - Oncogene

IS - 26

ER -