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

Oncogene. 2019 Jun;38(26):5127-5141. doi: 10.1038/s41388-019-0783-9. Epub 2019 Mar 14.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • HeLa Cells
  • High-Throughput Nucleotide Sequencing
  • Humans
  • MCF-7 Cells
  • Microarray Analysis
  • RNA Interference / physiology
  • RNA, Long Noncoding / genetics*
  • Sequence Analysis, RNA

Substances

  • RNA, Long Noncoding