SIDT2 RNA Transporter Promotes Lung and Gastrointestinal Tumor Development

RNautophagy is a newly-described type of selective autophagy whereby cellular RNAs are transported into lysosomes for degradation. This process involves the transmembrane protein SIDT2, which transports double-stranded RNA (dsRNA) across the endolysosomal membrane. We previously demonstrated that SIDT2 is a transcriptional target of p53, but its role in tumorigenesis – if any - is unclear. Unexpectedly, we show here that Sidt2−/− mice with concurrent oncogenic KrasG12D activation develop significantly fewer tumors than littermate controls in a mouse model of lung adenocarcinoma (LUAD). Consistent with this observation, loss of SIDT2 also leads to enhanced survival and delayed tumor development in an Apcmin/+ mouse model of intestinal cancer. Within the intestine, Apcmin/+;Sidt2−/− mice display accumulation of dsRNA in association with increased phosphorylation of eIF2α and JNK as well as elevated rates of apoptosis. Taken together, our data demonstrate a role for SIDT2 - and by extension RNautophagy - in promoting tumor development.

• Publication year

  2019

• Venue

  bioRxiv

• Publication date

  2019-08-07

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1016/j.isci.2019.09.009PMID 31546103PMCID 6817685
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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