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bioRxiv · 10.1101/724237

SIDT2 RNA transporter promotes lung and gastrointestinal tumor development

Nguyen, T.·Bieging-Rolett, K.·Putoczki, T.·Wicks, I.·Attardi, L.·Pang, K.
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Abstract

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 eIF2 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.

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Nguyen, T., Bieging-Rolett, K., Putoczki, T., Wicks, I., Attardi, L., Pang, K.. 2019-08-07. SIDT2 RNA transporter promotes lung and gastrointestinal tumor development. https://doi.org/10.1101/724237

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