Emerging relationship between RNA helicases and autophagy

Abstract

RNA helicases, the largest family of proteins that participate in RNA metabolism, stabilize the intracellular environment through various processes, such as translation and pre-RNA splicing. These proteins are also involved in some diseases, such as cancers and viral diseases. Autophagy, a self-digestive and cytoprotective trafficking process in which superfluous organelles and cellular garbage are degraded to stabilize the internal environment or maintain basic cellular survival, is associated with human diseases. Interestingly, similar to autophagy, RNA helicases play important roles in maintaining cellular homeostasis and are related to many types of diseases. According to recent studies, RNA helicases are closely related to autophagy, participate in regulating autophagy, or serve as a bridge between autophagy and other cellular activities that widely regulate some pathophysiological processes or the development and progression of diseases. Here, we summarize the most recent studies to understand how RNA helicases function as regulatory proteins and determine their association with autophagy in various diseases.

Keywords: RNA helicase; Autophagy; Homeostasis; Regulation.

Fig. 1

Regulation of autophagy by RNA helicases at different stages DEAD(Asp–Glu–Ala–Asp)-box helicase 6 (DDX6) suppresses autophagy by degrading autophagy-related (ATG) protein messenger RNAs (mRNAs) when nutrients are adequate. DDX5 interacts with p62 to inhibit mammalian target of rapamycin (mTOR) and then activate autophagy. DDX17 reduces the expression of Beclin1 by increasing miR-34-5p and miR-5195-3p expression. DDX53 promotes autophagy by increasing the expression of ATG5 and then increasing the conversion of microtubule-associated protein 1 light chain 3-I (LC3-I) to LC3-II. TRAF6: tumor necrosis factor (TNF) receptor-associated factor 6; P: phosphorylation; Dcp2: decapping enzyme; UTR: untranslated region

Fig. 2

RNA helicase and autophagy associated with cell death or diseases DEAD-box RNA helicases directly regulate autophagy, which can be relevant to drug tolerance of cancer and tumorigenesis such as HCC and glioma. Virus-induced autophagy and other immune inhibitor-induced autophagy repress RIG-I, which benefits to viral replication and immune responses. [pIC]^PEI-induced autophagy is associated with MDA5, which contributes to cell death. DEAD: Asp–Glu–Ala–Asp; HCC: hepatocellular carcinoma; RIG-I: retinoic acid-inducible gene I; [pIC]^PEI: the double-stranded RNA (dsRNA) mimic polyinosinic-polycytidylic acid (pIC) coadministered with polyethyleneimine (PEI) as a carrier; MDA5: melanoma differentiation-associated 5; BST2: bone marrow stromal cell antigen 2; LRRC25: leucine-rich repeat containing protein 25; RLR: RIG-I-like receptor