Zinc finger 1 of the RING E3 ligase, RNF125, interacts with the E2 to enhance ubiquitylation

Middleton, Adam J.; Barzak, Fareeda M; Fokkens, Thornton J; Nguyen, Khanh Q.; Day, Catherine L.

doi:10.1016/j.str.2023.07.007

Cited by 2 publications

(3 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The RING and first ZF domain of RNF125 are required for ubiquitin transfer and some disease associated variants in these domains clearly impede the E3 ligase activity. 16,18 It is less clear how other reported variants alter RNF125 function, although it has been suggested that they impact substrate binding or cellular stability. 16 Our analysis of RNF125 in which glutamate 224 has been substituted by glutamine indicates that this change does not alter E3 ligase activity.…”

Section: Discussionmentioning

confidence: 99%

“…We expressed and purified recombinant wild-type and Glu224Gln RNF125 proteins and incubated them with the promiscuous E2 ubiquitin-conjugating enzyme, UbcH5b, which is known to promote formation of ubiquitin chains when paired with RNF125. 18 The assay also included the ubiquitin activating E1 enzyme, and both unlablled and labelled ubiquitin which allowed activity to be readily monitored. Analysis of ubiquitin chain assembly by SDS-PAGE showed that the Glu224Gln substitution did not compromise the E3 ligase activity of RNF125 (Figure 2B and Figure S1).…”

Section: Ubiquitin Transfer Activity Of Rnf125 Variantsmentioning

confidence: 99%

“…This result is consistent with recent studies that have shown that the RING and ZF1 domains of RNF125 interact with E2 enzymes and are sufficient for the assembly of ubiquitin chains. 16,18 However, within cells modification of the correct substrate is required and mutations C-terminal to ZF1 may disrupt substrate recruitment by RNF125.…”

Section: Ubiquitin Transfer Activity Of Rnf125 Variantsmentioning

confidence: 99%

See 2 more Smart Citations

A novel RNF125 variant associated with Tenorio syndrome alters ubiquitin chain binding

Barzak,

Lu,

Geltzeiler

et al. 2023

Clinical Genetics

Self Cite

View full text Add to dashboard Cite

A key signalling pathway required for clearance of viruses from host cells relies on the receptor protein, retinoic acid‐inducible gene I (RIG‐I). The activity of RIG‐I is tightly controlled, and once bound to viral dsRNA, addition of lysine 63‐linked ubiquitin chains activates signalling. Meanwhile, the addition of lysine 48‐linked ubiquitin chains to RIG‐I is required to terminate signalling when the infection has been resolved. Really interesting new gene (RING) finger protein 125 (RNF125) is the E3 ligase responsible for addition of the ubiquitin chains that terminate signalling, with disruption of its function associated with Tenorio syndrome. Here we describe a novel RNF125 gene variant in an individual with clinical symptoms including intellectual disability, macrocephaly and congenital heart disease, consistent with Tenorio syndrome. The newly identified Tenorio syndrome‐associated variant [(NM_017831.4):c.670G>C p.Glu224Gln] is the first to be found in the ubiquitin interaction motif (UIM) of RNF125. While the E3 ligase activity of this RNF125 variant is retained, it has an impaired ability to interact with lysine 63‐linked ubiquitin chains. The function of the UIM in RNF125 is uncertain; however, this study suggests that the UIM binds lysine 63‐linked ubiquitin chains, and that this interaction is required for the normal function of RNF125.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Ubiquitin Transfer Activity Of Rnf125 Variantsmentioning

confidence: 99%

Section: Ubiquitin Transfer Activity Of Rnf125 Variantsmentioning

confidence: 99%

See 1 more Smart Citation

A novel RNF125 variant associated with Tenorio syndrome alters ubiquitin chain binding

Barzak,

Lu,

Geltzeiler

et al. 2023

Clinical Genetics

Self Cite

View full text Add to dashboard Cite

show abstract

Structural basis for RNA polymerase II ubiquitylation and inactivation in transcription-coupled repair

Kokic,

Yakoub,

van den Heuvel

et al. 2024

Nat Struct Mol Biol

Self Cite

View full text Add to dashboard Cite

During transcription-coupled DNA repair (TCR), RNA polymerase II (Pol II) transitions from a transcriptionally active state to an arrested state that allows for removal of DNA lesions. This transition requires site-specific ubiquitylation of Pol II by the CRL4CSA ubiquitin ligase, a process that is facilitated by ELOF1 in an unknown way. Using cryogenic electron microscopy, biochemical assays and cell biology approaches, we found that ELOF1 serves as an adaptor to stably position UVSSA and CRL4CSA on arrested Pol II, leading to ligase neddylation and activation of Pol II ubiquitylation. In the presence of ELOF1, a transcription factor IIS (TFIIS)-like element in UVSSA gets ordered and extends through the Pol II pore, thus preventing reactivation of Pol II by TFIIS. Our results provide the structural basis for Pol II ubiquitylation and inactivation in TCR.

show abstract

Zinc finger 1 of the RING E3 ligase, RNF125, interacts with the E2 to enhance ubiquitylation

Cited by 2 publications

References 55 publications

A novel RNF125 variant associated with Tenorio syndrome alters ubiquitin chain binding

A novel RNF125 variant associated with Tenorio syndrome alters ubiquitin chain binding

Structural basis for RNA polymerase II ubiquitylation and inactivation in transcription-coupled repair

Contact Info

Product

Resources

About