UPF1 adds an m6A feather to its (de)cap

Gibbs, Michelle R.; Chanfreau, Guillaume

doi:10.1016/j.celrep.2022.110898

Cited by 3 publications

(5 citation statements)

References 8 publications

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“…The installed m 6 A is selectively recognized by m 6 A reader proteins, such as YTHDF1, YTHDF2, and YTHDF3, and consequently affects diverse molecular events 23 – 25 , 27 – 29 . As mentioned above, the UPF1-YTHDF2 interaction promotes decapping, followed by 5′–3′ degradation of YTHDF2-bound m 6 A mRNAs 19 , 20 .…”

Section: Introductionmentioning

confidence: 74%

“…A recent study showed that YTHDF2 interacts with UPF1 19 , 20 , which guides proper targeting of misfolded polypeptides to the aggresome 16 . This interaction led us to investigate the possible connection between m 6 A modification and aggresome formation.…”

Section: Resultsmentioning

confidence: 99%

“…UPF1 is a multi-talented protein involved in NMD and many other mRNA decay pathways 15 . Recently, it was also reported that UPF1 triggers the rapid degradation of RNAs containing N 6 -methyladenosine (m 6 A; modified adenosine with a methyl group at the 6 th position of the amino group) through its direct interaction with an m 6 A-reader protein, YT521-B homology domain-containing family protein 2 (YTHDF2) 19 , 20 . The m 6 A modification is the most abundant internal mRNA modification.…”

Section: Introductionmentioning

confidence: 99%

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YTHDF2 facilitates aggresome formation via UPF1 in an m6A-independent manner

Hwang,

Park,

Kim

et al. 2023

Nat Commun

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YTHDF2 has been extensively studied and typified as an RNA-binding protein that specifically recognizes and destabilizes RNAs harboring N6-methyladenosine (m6A), the most prevalent internal modification found in eukaryotic RNAs. In this study, we unravel the m6A-independent role of YTHDF2 in the formation of an aggresome, where cytoplasmic protein aggregates are selectively sequestered upon failure of protein homeostasis mediated by the ubiquitin-proteasome system. Downregulation of YTHDF2 in HeLa cells reduces the circularity of aggresomes and the rate of movement of misfolded polypeptides, inhibits aggresome formation, and thereby promotes cellular apoptosis. Mechanistically, YTHDF2 is recruited to a misfolded polypeptide-associated complex composed of UPF1, CTIF, eEF1A1, and DCTN1 through its interaction with UPF1. Subsequently, YTHDF2 increases the interaction between the dynein motor protein and the misfolded polypeptide-associated complex, facilitating the diffusion dynamics of the movement of misfolded polypeptides toward aggresomes. Therefore, our data reveal that YTHDF2 is a cellular factor involved in protein quality control.

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Section: Introductionmentioning

confidence: 74%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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YTHDF2 facilitates aggresome formation via UPF1 in an m6A-independent manner

Hwang,

Park,

Kim

et al. 2023

Nat Commun

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“…promotes rapid degradation of m6A-containing RNAs 25 . LncRNAs also regulate the post-transcriptional processes of mRNA degradation 26 .…”

Section: Discussionmentioning

confidence: 99%

Deficiency of LncRNA-CIRBIL promotes J-wave syndrome by enhancing transmural heterogeneity of Ito current

Jin

Zhang

et al. 2022

Preprint

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Transmural heterogeneity of Ito current is a major cause of J-wave syndrome (JWS), while the underlying molecular mechanisms remain elusive. The present study aims to explore the influence of Cardiac Injury-Related Bclaf1-Interacting LncRNA (lncCIRBIL) on cardiac J-wave syndrome and to delineate the molecular mechanisms. The plasma level of lncCIRBIL was reduced in JWS patients and cold-induced JWS mice. Knockout of lncCIRBIL increased the frequency of J-wave and the susceptibility to ventricular arrhythmia in mice. The transmural difference of KCND2 and Ito currents were dramatically increased in the right ventricle, but not the left ventricle of lncCIRBIL-KO mice. In contrast, cardiomyocyte-specific transgenic overexpression of lncCIRBIL produced the opposite effects. The human homologous conserved fragment of lncCIRBIL (hcf-CIRBIL) reduced Ito, downregulated action potential notch and prolonged APD20 in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). LncCIRBIL titrates the transmural heterogeneity of KCND2 by regulating UPF1 mediated mRNA decay. Inhibition of lncCIRBIL promoted J-wave syndrome by enhancing the transmural heterogeneity of Ito in the right ventricle. These findings imply that lncCIRBIL represents a potential therapeutic target for J-wave syndrome.

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“…Recent studies have provided molecular insights into the rapid degradation of m 6 A mRNAs (Boo et al, 2022;Boo and Kim, 2020;Du et al, 2016;Gibbs and Chanfreau, 2022;Lee et al, 2020;Park et al, 2019;Wang et al, 2014). When YTHDF2 recognizes m 6 A, it preferentially elicits deadenylation, followed by 3 0 -to-5 0 degradation of m 6 A mRNAs by recruiting the CCR4/NOT deadenylase complex (Du et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

UPF1 adds an m6A feather to its (de)cap

Cited by 3 publications

References 8 publications

YTHDF2 facilitates aggresome formation via UPF1 in an m6A-independent manner

YTHDF2 facilitates aggresome formation via UPF1 in an m6A-independent manner

Deficiency of LncRNA-CIRBIL promotes J-wave syndrome by enhancing transmural heterogeneity of Ito current

m1A and m6A modifications function cooperatively to facilitate rapid mRNA degradation

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