Continuous synthesis and degradation of RNAs are important for cellular homeostasis. Tomohiro Kabuta and colleagues have previously identified the degradation of RNA and DNA by autophagy, which they termed RNautophagy/DNautophagy (RDA), and demonstrated a role for the putative nuclei acid transporter SID-1 transmembrane family member 2 (SIDT2) in mediating the translocation of RNA or DNA across the lysosomal membrane. However, several aspects of SIDT2 function in RDA remained unclear, including how it is sorted to lysosomes, because unlike other lysosomal proteins, it does not contain a potential sorting motif in its cytoplasmic C-terminus. In this work (p. 2843), the authors now show that overexpression of SIDT2 in cells considerably increases the degradation of endogenous RNAs via RDA, which, to their knowledge, is the first report of an endogenous protein that when overexpressed enhances cellular RNA degradation. With regard to the targeting of SIDT2, the authors identify three cytosolic YxxΦ motifs that are required to localise it to the lysosome and to exert its function in RDA. In addition, they also report that SIDT2 interacts with the adaptor complexes AP-1 and AP-2. Thus, this work establishes SIDT2 as a key factor in maintaining cellular RNA homeostasis that might also be exploited as a potential target for the development of novel therapies for diseases associated with toxic RNA accumulation.

• © 2017. Published by The Company of Biologists Ltd