Work

SIDT2 RNA Transporter Promotes Lung and Gastrointestinal Tumor Development

Year: 2019

Type: article

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 Kras G12D activation develop significantly fewer tumors than littermate controls in a mouse model of lung adenocarcinoma. Consistent with this observation, loss of SIDT2 also leads to enhanced survival and delayed tumor development in an Apc min/+ mouse model of intestinal cancer. Within the intestine, Apc min/+ ; 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.

Source: iScience

DOI: 10.1016/j.isci.2019.09.009

Authors: Tan A. Nguyen, Kathryn T. Bieging-Rolett, Tracy L. Putoczki, Ian P. Wicks, Laura D. Attardi, Ken C. Pang