Roles and mechanisms of the m6A reader YTHDC1 in biological processes and diseases

Yan, Huaqing; Zhang, Liqi; Cui, Xiaobo; Zheng, Sinian; Li, Rubing

doi:10.1038/s41420-022-01040-2

Cited by 46 publications

(34 citation statements)

References 63 publications

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“…Furthermore, even though YTHDC1 and DDX5 46 , 47 are both nuclear factors, we ruled out that the observed reduction of circRNAs could be related to their reduced stability by performing actinomycin D treatment in RD cells. As expected, besides the high stability of circRNAs over time (up to 12 hrs), we did not observe reduced half-life either upon YTHDC1 nor in DDX5 depletion (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

The m6A reader YTHDC1 and the RNA helicase DDX5 control the production of rhabdomyosarcoma-enriched circRNAs

et al. 2023

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N6-Methyladenosine (m6A) is well-known for controlling different processes of linear RNA metabolism. Conversely, its role in the biogenesis and function of circular RNAs (circRNAs) is still poorly understood. Here, we characterize circRNA expression in the pathological context of rhabdomyosarcoma (RMS), observing a global increase when compared to wild-type myoblasts. For a set of circRNAs, such an increase is due to the raised expression of the m6A machinery, which we also find to control the proliferation activity of RMS cells. Furthermore, we identify the RNA helicase DDX5 as a mediator of the back-splicing reaction and as a co-factor of the m6A regulatory network. DDX5 and the m6A reader YTHDC1 are shown to interact and to promote the production of a common subset of circRNAs in RMS. In line with the observation that YTHDC1/DDX5 depletion reduces RMS proliferation, our results provide proteins and RNA candidates for the study of rhabdomyosarcoma tumorigenicity.

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Section: Resultsmentioning

confidence: 99%

The m6A reader YTHDC1 and the RNA helicase DDX5 control the production of rhabdomyosarcoma-enriched circRNAs

et al. 2023

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“…YTHDC1, one of the most noted m 6 A reader, recognizes m 6 A modification on mRNAs or ncRNAs and mediates different biological processes, such as cytoplasmic export, RNA stabilization and decay [ 39 ]. Notably, YTHDC1 plays critical roles in different cancers [ 39 , 40 ], and the elevation of YTHDC1 is observed in CRC cells and tissues [ 41 ]. Recent studies have demonstrated that YTHDC1 facilitates cytoplasmic delivery of circMET in renal cell carcinoma [ 42 ], as well as the cytoplasmic translocation of circHPS5 in hepatocellular carcinoma (HCC) in an m 6 A-dependent manner [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

“…m 6 A modification is originally identified as a predominant modification of mRNA, and its pivotal roles in ncRNA modification have emerged recently [4,5]. YTHDC1, one of the most noted m 6 A reader, recognizes m 6 A modification on mRNAs or ncRNAs and mediates different biological processes, such as cytoplasmic export, RNA stabilization and decay [39]. Notably, YTHDC1 plays critical roles in different cancers [39,40], and the elevation of YTHDC1 is observed in CRC cells and tissues [41].…”

Section: Discussionmentioning

confidence: 99%

m6A-modified circFNDC3B inhibits colorectal cancer stemness and metastasis via RNF41-dependent ASB6 degradation

et al. 2022

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Colorectal cancer (CRC) is the third most frequently diagnosed cancer with unfavorable clinical outcomes worldwide. circFNDC3B plays as a tumor suppressor in CRC, however, the mechanism of circFNDC3B in CRC remains ambiguous. The stem-like properties of CRC cells were detected by the evaluation of stemness markers, sphere formation assay and flow cytometry. qRT-PCR, FISH, IHC, and western blotting assessed the expression and localization of circFNDC3B, RNF41, ASB6, and stemness markers in CRC. The metastatic capabilities of CRC cells were examined by wound healing and Transwell assays, as well as in vivo liver metastasis model. Bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down assay and co-IP were used to detect the associations among circFNDC3B, FXR2, RNF41, and ASB6. Downregulated circFNDC3B was associated with unfavorite survival in CRC patients, and circFNDC3B overexpression suppressed CRC stemness and metastasis. Mechanistically, studies revealed that YTHDC1 facilitated cytoplasmic translocation of m6A-modified circFNDC3B, and circFNDC3B enhanced RNF41 mRNA stability and expression via binding to FXR2. circFNDC3B promoted ASB6 degradation through RNF41-mediated ubiquitination. Functional studies showed that silencing of RNF41 counteracted circFNDC3B-suppressed CRC stemness and metastasis, and ASB6 overexpression reversed circFNDC3B- or RNF41-mediated regulation of CRC stemness and metastasis. Elevated ASB6 was positively correlated with unfavorite survival in CRC patients. In vivo experiments further showed that circFNDC3B or RNF41 overexpression repressed tumor growth, stemness and liver metastasis via modulating ASB6. Taken together, m6A-modified circFNDC3B inhibited CRC stemness and metastasis via RNF41-dependent ASB6 degradation. These findings provide novel insights and important clues for targeted therapeutic strategies of CRC.

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“…Currently, there are three RBPs that have been widely studied, including YT521-B homology (YTH) domain family proteins, insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) and heterogeneous nuclear ribonucleoproteins (HNRNP) family proteins ( Liu C. et al, 2022 ). The YTH domain family proteins are important m6A methylation RBPs, which can bind to m6A and affect the outcome of m6A-methylated RNAs ( Yan et al, 2022 ). YTH proteins mainly includes YTHDFs and YTHDCs subtypes.…”

Section: Abnormal Expression Of N6-methyladenosine Modification Prote...mentioning

confidence: 99%

Crosstalk among N6-methyladenosine modification and RNAs in central nervous system injuries

Tian

Mao

Zhang

2022

Front. Cell. Neurosci.

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Central nervous system (CNS) injuries, including traumatic brain injury (TBI), intracerebral hemorrhage (ICH) and ischemic stroke, are the most common cause of death and disability around the world. As the most common modification on ribonucleic acids (RNAs), N6-methyladenosine (m6A) modification has recently attracted great attentions due to its functions in determining the fate of RNAs through changes in splicing, translation, degradation and stability. A large number of studies have suggested that m6A modification played an important role in brain development and involved in many neurological disorders, particularly in CNS injuries. It has been proposed that m6A modification could improve neurological impairment, inhibit apoptosis, suppress inflammation, reduce pyroptosis and attenuate ferroptosis in CNS injuries via different molecules including phosphatase and tensin homolog (PTEN), NLR family pyrin domain containing 3 (NLRP3), B-cell lymphoma 2 (Bcl-2), glutathione peroxidase 4 (GPX4), and long non-coding RNA (lncRNA). Therefore, m6A modification showed great promise as potential targets in CNS injuries. In this article, we present a review highlighting the role of m6A modification in CNS injuries. Hence, on the basis of these properties and effects, m6A modification may be developed as therapeutic agents for CNS injury patients.

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Roles and mechanisms of the m6A reader YTHDC1 in biological processes and diseases

Cited by 46 publications

References 63 publications

The m6A reader YTHDC1 and the RNA helicase DDX5 control the production of rhabdomyosarcoma-enriched circRNAs

The m6A reader YTHDC1 and the RNA helicase DDX5 control the production of rhabdomyosarcoma-enriched circRNAs

m6A-modified circFNDC3B inhibits colorectal cancer stemness and metastasis via RNF41-dependent ASB6 degradation

Crosstalk among N6-methyladenosine modification and RNAs in central nervous system injuries

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