CSDE1 controls gene expression through the miRNA-mediated decay machinery

Kakumani, Pavan Kumar; Harvey, Louis-Mathieu; Houle, François; Guitart, Tanit; Gebauer, Fátima; Simard, Martin J.

doi:http://dx.doi.org/10.26508/lsa.201900632

CSDE1 controls gene expression through the miRNA-mediated decay machinery

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Kakumani PK, Harvey LM, Houle F, Guitart T, Gebauer F, Simard MJ. CSDE1 controls gene expression through the miRNA-mediated decay machinery. Life Sci Alliance. 2020; 3(4). pii: e201900632. DOI: 10.26508/lsa.201900632

Abstract

In animals, miRNAs are the most prevalent small non-coding RNA molecules controlling posttranscriptional gene regulation. The Argonaute proteins (AGO) mediate miRNA-guided gene silencing by recruiting multiple factors involved in translational repression, deadenylation, and decapping. Here, we report that CSDE1, an RNA-binding protein linked to stem cell maintenance and metastasis in cancer, interacts with AGO2 within miRNA-induced silencing complex and mediates gene silencing through its N-terminal domains. We show that CSDE1 interacts with LSM14A, a constituent of P-body assembly and further associates to the DCP1-DCP2 decapping complex, suggesting that CSDE1 could promote the decay of miRNA-induced silencing complex-targeted mRNAs. Together, our findings uncover a hitherto unknown mechanism used by CSDE1 in the control of gene expression mediated by the miRNA pathway.