Full Text:   <1843>

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CLC number: R34

On-line Access: 2020-10-12

Received: 2020-05-10

Revision Accepted: 2020-08-10

Crosschecked: 2020-09-07

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Citations:  Bibtex RefMan EndNote GB/T7714


Zheng-gang Yang


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Journal of Zhejiang University SCIENCE B 2020 Vol.21 No.10 P.767-778


Emerging relationship between RNA helicases and autophagy

Author(s):  Miao-miao Zhao, Ru-sha Wang, Yan-lin Zhou, Zheng-gang Yang

Affiliation(s):  The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; more

Corresponding email(s):   yangzg@zju.edu.cn

Key Words:  RNA helicase, Autophagy, Homeostasis, Regulation

Miao-miao Zhao, Ru-sha Wang, Yan-lin Zhou, Zheng-gang Yang. Emerging relationship between RNA helicases and autophagy[J]. Journal of Zhejiang University Science B, 2020, 21(10): 767-778.

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author="Miao-miao Zhao, Ru-sha Wang, Yan-lin Zhou, Zheng-gang Yang",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Emerging relationship between RNA helicases and autophagy
%A Miao-miao Zhao
%A Ru-sha Wang
%A Yan-lin Zhou
%A Zheng-gang Yang
%J Journal of Zhejiang University SCIENCE B
%V 21
%N 10
%P 767-778
%@ 1673-1581
%D 2020
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2000245

T1 - Emerging relationship between RNA helicases and autophagy
A1 - Miao-miao Zhao
A1 - Ru-sha Wang
A1 - Yan-lin Zhou
A1 - Zheng-gang Yang
J0 - Journal of Zhejiang University Science B
VL - 21
IS - 10
SP - 767
EP - 778
%@ 1673-1581
Y1 - 2020
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2000245

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.



Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Ahmad S, Mu X, Yang F, et al., 2018. Breaching self-tolerance to Alu duplex RNA underlies MDA5-mediated inflammation. Cell, 172(4):797-810.e13.

[2]Becher P, Avalos Ramirez R, Orlich M, et al., 2003. Genetic and antigenic characterization of novel pestivirus genotypes: implications for classification. Virology, 311(1):96-104.

[3]Chan YK, Gack MU, 2015. RIG-I-like receptor regulation in virus infection and immunity. Curr Opin Virol, 12:7-14.

[4]Cho B, Lim Y, Lee DY, et al., 2002. Identification and characterization of a novel cancer/testis antigen gene CAGE. Biochem Biophys Res Commun, 292(3):715-726.

[5]Corti O, 2019. Neuronal mitophagy: lessons from a pathway linked to Parkinson’s disease. Neurotox Res, 36(2):292-305.

[6]Devarkar SC, Schweibenz B, Wang C, et al., 2018. RIG-I uses an ATPase-powered translocation-throttling mechanism for kinetic proofreading of RNAs and oligomerization. Mol Cell, 72(2):355-368.e4.

[7]Du Y, Duan TH, Feng YC, et al., 2018. LRRC25 inhibits type I IFN signaling by targeting ISG15-associated RIG-I for autophagic degradation. EMBO J, 37(3):351-366.


[9]Duprez L, Wirawan E, Vanden Berghe T, et al., 2009. Major cell death pathways at a glance. Microbes Infect, 11(13):1050-1062.

[10]Fang SC, Su JM, Liang BY, et al., 2017. Suppression of autophagy by mycophenolic acid contributes to inhibition of HCV replication in human hepatoma cells. Sci Rep, 7: 44039.

[11]Frankel LB, Lubas M, Lund AH, 2017. Emerging connections between RNA and autophagy. Autophagy, 13(1):3-23.

[12]Gorbalenya AE, Koonin EV, 1993. Helicases: amino acid sequence comparisons and structure-function relationships. Curr Opin Struct Biol, 3(3):419-429.

[13]Hardwick SW, Luisi BF, 2013. Rarely at rest: RNA helicases and their busy contributions to RNA degradation, regulation and quality control. RNA Biol, 10(1):56-70.

[14]Hashemi V, Masjedi A, Hazhir-Karzar B, et al., 2019. The role of DEAD-box RNA helicase p68 (DDX5) in the development and treatment of breast cancer. J Cell Physiol, 234(5):5478-5487.

[15]Hu GW, McQuiston T, Bernard A, et al., 2015. A conserved mechanism of TOR-dependent RCK-mediated mRNA degradation regulates autophagy. Nat Cell Biol, 17(7):930-942.

[16]Huang WJ, Zhao FR, Huang Y, et al., 2014. Rapamycin enhances HBV production by inducing cellular autophagy. Hepat Mon, 14(10):e20719.

[17]Inao T, Harashima N, Monma H, et al., 2012. Antitumor effects of cytoplasmic delivery of an innate adjuvant receptor ligand, poly(I:C), on human breast cancer. Breast Cancer Res Treat, 134(1):89-100.

[18]Ito S, Koso H, Sakamoto K, et al., 2017. RNA helicase DHX15 acts as a tumour suppressor in glioma. Br J Cancer, 117(9):1349-1359.

[19]Iwata T, Fujita T, Hirao N, et al., 2005. Frequent immune responses to a cancer/testis antigen, CAGE, in patients with microsatellite instability-positive endometrial cancer. Clin Cancer Res, 11(10):3949-3957.

[20]Jankowsky E, 2011. RNA helicases at work: binding and rearranging. Trends Biochem Sci, 36(1):19-29.

[21]Jarmoskaite I, Russell R, 2014. RNA helicase proteins as chaperones and remodelers. Annu Rev Biochem, 83:697-725.

[22]Jin SH, Cui J, 2018. BST2 inhibits type I IFN (interferon) signaling by accelerating MAVS degradation through CALCOCO2-directed autophagy. Autophagy, 14(1):171-172.

[23]Jing Y, Nguyen MM, Wang D, et al., 2018. DHX15 promotes prostate cancer progression by stimulating Siah2-mediated ubiquitination of androgen receptor. Oncogene, 37(5):638-650.

[24]Jounai N, Takeshita F, Kobiyama K, et al., 2007. The Atg5– Atg12 conjugate associates with innate antiviral immune responses. Proc Natl Acad Sci USA, 104(35):14050-14055.

[25]Kaniuk NA, Kiraly M, Bates H, et al., 2007. Ubiquitinated-protein aggregates form in pancreatic β-cells during diabetes-induced oxidative stress and are regulated by autophagy. Diabetes, 56(4):930-939.

[26]Kao SH, Cheng WC, Wang YT, et al., 2019. Regulation of miRNA biogenesis and histone modification by K63-polyubiquitinated DDX17 controls cancer stem-like features. Cancer Res, 79(10):2549-2563.

[27]Kato H, Sato S, Yoneyama M, et al., 2005. Cell type-specific involvement of RIG-I in antiviral response. Immunity, 23(1):19-28.

[28]Ke PY, Chen SSL, 2011. Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro. J Clin Invest, 121(1):37-56.

[29]Kim H, Kim Y, Jeoung D, 2017. DDX53 promotes cancer stem cell-like properties and autophagy. Mol Cells, 40(1):54-65.


[31]Lan SH, Wu SY, Zuchini R, et al., 2014. Autophagy suppresses tumorigenesis of hepatitis B virus-associated hepatocellular carcinoma through degradation of microRNA-224. Hepatology, 59(2):505-517.

[32]Leitão AL, Costa MC, Enguita FJ, 2015. Unzippers, resolvers and sensors: a structural and functional biochemistry tale of RNA helicases. Int J Mol Sci, 16(2):2269-2293.

[33]Linares JF, Duran A, Yajima T, et al., 2013. K63 polyubiquitination and activation of mTOR by the p62-TRAF6 complex in nutrient-activated cells. Mol Cell, 51(3):283-296.

[34]Linder P, 2006. Dead-box proteins: a family affair—active and passive players in RNP-remodeling. Nucleic Acids Res, 34(15):4168-4180.

[35]Linder P, Jankowsky E, 2011. From unwinding to clamping— the DEAD box RNA helicase family. Nat Rev Mol Cell Biol, 12(8):505-516.

[36]Liu X, Yao ZY, Jin MY, et al., 2019. Dhh1 promotes autophagy-related protein translation during nitrogen starvation. PLoS Biol, 17(4):e3000219.

[37]Loo YM, Gale M Jr, 2011. Immune signaling by RIG-I-like receptors. Immunity, 34(5):680-692.

[38]Ma ZC, Feng J, Guo YR, et al., 2017. Knockdown of DDX5 inhibits the proliferation and tumorigenesis in esophageal cancer. Oncol Res, 25(6):887-895.

[39]Melchjorsen J, Jensen SB, Malmgaard L, et al., 2005. Activation of innate defense against a paramyxovirus is mediated by RIG-I and TLR7 and TLR8 in a cell-type-specific manner. J Virol, 79(20):12944-12951.

[40]Miller S, Krijnse-Locker J, 2008. Modification of intracellular membrane structures for virus replication. Nat Rev Microbiol, 6(5):363-374.

[41]Moscat J, Karin M, Diaz-Meco MT, 2016. p62 in cancer: signaling adaptor beyond autophagy. Cell, 167(3):606-609.

[42]Ozgur S, Buchwald G, Falk S, et al., 2015. The conformational plasticity of eukaryotic RNA-dependent ATPases. FEBS J, 282(5):850-863.

[43]Pattabhi S, Knoll ML, Gale M Jr, et al., 2019. DHX15 is a coreceptor for RLR signaling that promotes antiviral defense against RNA virus infection. J Interferon Cytokine Res, 39(6):331-346.

[44]Pei JJ, Deng JR, Ye ZD, et al., 2016. Absence of autophagy promotes apoptosis by modulating the ROS-dependent RLR signaling pathway in classical swine fever virus-infected cells. Autophagy, 12(10):1738-1758.

[45]Presnyak V, Coller J, 2013. The DHH1/RCKp54 family of helicases: an ancient family of proteins that promote translational silencing. Biochim Biophys Acta, 1829(8):817-823.

[46]Putnam AA, Jankowsky E, 2013. DEAD-box helicases as integrators of RNA, nucleotide and protein binding. Biochim Biophys Acta, 1829(8):884-893.

[47]Ravikumar B, Sarkar S, Davies JE, et al., 2010. Regulation of mammalian autophagy in physiology and pathophysiology. Physiol Rev, 90(4):1383-1435.

[48]Rocak S, Linder P, 2004. DEAD-box proteins: the driving forces behind RNA metabolism. Nat Rev Mol Cell Biol, 5(3):232-241.

[49]Rodriguez KR, Bruns AM, Horvath CM, 2014. MDA5 and LGP2: accomplices and antagonists of antiviral signal transduction. J Virol, 88(15):8194-8200.

[50]Santiago FW, Covaleda LM, Sanchez-Aparicio MT, et al., 2014. Hijacking of RIG-I signaling proteins into virus-induced cytoplasmic structures correlates with the inhibition of type I interferon responses. J Virol, 88(8):4572-4585.

[51]Sha M, Lin M, Wang J, et al., 2018. Long non-coding RNA MIAT promotes gastric cancer growth and metastasis through regulation of miR-141/DDX5 pathway. J Exp Clin Cancer Res, 37:58.

[52]Singleton MR, Dillingham MS, Wigley DB, 2007. Structure and mechanism of helicases and nucleic acid translocases. 76:23-50.

[53]Su CJ, Feng Y, Liu TT, et al., 2017. Thioredoxin-interacting protein induced α-synuclein accumulation via inhibition of autophagic flux: implications for Parkinson’s disease. CNS Neurosci Ther, 23(9):717-723.

[54]Sutton MN, Yang HL, Huang GY, et al., 2018. RAS-related GTPases DIRAS1 and DIRAS2 induce autophagic cancer cell death and are required for autophagy in murine ovarian cancer cells. Autophagy, 14(4):637-653.

[55]Szabo A, Magyarics Z, Pazmandi K, et al., 2014. TLR ligands upregulate RIG-I expression in human plasmacytoid dendritic cells in a type I IFN-independent manner. Immunol Cell Biol, 92(8):671-678.

[56]Takeuchi O, Akira S, 2008. MDA5/RIG-I and virus recognition. Curr Opin Immunol, 20(1):17-22.

[57]Tal MC, Sasai M, Lee HK, et al., 2009. Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling. Proc Natl Acad Sci USA, 106(8):2770-2775.

[58]Teodorof-Diedrich C, Spector SA, 2018. Human immunodeficiency virus type 1 gp120 and Tat induce mitochondrial fragmentation and incomplete mitophagy in human neurons. J Virol, 92(22):e00993-18.

[59]Tormo D, Checinska A, Alonso-Curbelo D, et al., 2009. Targeted activation of innate immunity for therapeutic induction of autophagy and apoptosis in melanoma cells. Cancer Cell, 16(2):103-114.

[60]Tuteja N, Tuteja R, 2004. Unraveling DNA helicases. Motif, structure, mechanism and function. Eur J Biochem, 271(10):1849-1863.

[61]van Tongelen A, Loriot A, de Smet C, 2017. Oncogenic roles of DNA hypomethylation through the activation of cancer-germline genes. Cancer Lett, 396:130-137.

[62]Wang K, Klionsky DJ, 2011. Mitochondria removal by autophagy. Autophagy, 7(3):297-300.

[63]Wang PH, Zhu S, Yang L, et al., 2015. Nlrp6 regulates intestinal antiviral innate immunity. Science, 350(6262):826-830.

[64]Wang ZT, Lu MH, Zhang Y, et al., 2019. Disrupted-in-schizophrenia-1 protects synaptic plasticity in a transgenic mouse model of Alzheimer’s disease as a mitophagy receptor. Aging Cell, 18(1):e12860.

[65]Wen X, Klionsky DJ, 2016. An overview of macroautophagy in yeast. J Mol Biol, 428(9):1681-1699.

[66]Wu XL, Yang J, Na T, et al., 2017. RIG-I and IL-6 are negative-feedback regulators of STING induced by double-stranded DNA. PLoS ONE, 12(8):e0182961.

[67]Xia M, Gonzalez P, Li CY, et al., 2014. Mitophagy enhances oncolytic measles virus replication by mitigating DDX58/ RIG-I-like receptor signaling. J Virol, 88(9):5152-5164.

[68]Xu F, Li XB, Zhang PF, et al., 2016. Melanoma differentiation-associated gene 5 is involved in the induction of stress granules and autophagy by protonophore CCCP. Biol Chem, 397(1):67-74.

[69]Xu JZ, Zhang JL, Zhang WG, 2018. Antisense RNA: the new favorite in genetic research. J Zhejiang Univ Sci B (Biomed & Biotechnol), 19(10):739-749.

[70]Yang K, Wang J, Xiang AP, et al., 2013. Functional RIG-I-like receptors control the survival of mesenchymal stem cells. Cell Death Dis, 4(12):e967.

[71]Yang L, Li P, Fu SN, et al., 2010. Defective hepatic autophagy in obesity promotes ER stress and causes insulin resistance. Cell Metab, 11(6):467-478.

[72]Yang ZF, Klionsky DJ, 2010. Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol, 22(2):124-131.

[73]Ye WJ, Chew M, Hou J, et al., 2018. Microvesicles from malaria-infected red blood cells activate natural killer cells via MDA5 pathway. PLoS Pathog, 14(10):e1007298.

[74]Zhang H, Zhang YQ, Zhu XY, et al., 2019. DEAD box protein 5 inhibits liver tumorigenesis by stimulating autophagy via interaction with p62/SQSTM1. Hepatology, 69(3):1046-1063.

[75]Zhang ZX, Tian H, Miao Y, et al., 2016. Upregulation of p72 enhances malignant migration and invasion of glioma cells by repressing Beclin1 expression. Biochemistry (Moscow), 81(6):574-582.

[76]Zheng J, Wang C, Chang MR, et al., 2018. HDX-MS reveals dysregulated checkpoints that compromise discrimination against self RNA during RIG-I mediated autoimmunity. Nat Commun, 9:5366.

[77]Zhou H, Chen Y, Huang SW, et al., 2018. Regulation of autophagy by tea polyphenols in diabetic cardiomyopathy. J Zhejiang Univ Sci B (Biomed & Biotechnol), 19(5):333-341.

[78]Zhou RB, Yazdi AS, Menu P, et al., 2011. A role for mitochondria in NLRP3 inflammasome activation. Nature, 469(7329):221-225.

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