Reactome | RBBP6 activates CPSF complex

RBBP6 activates CPSF complex

Stable Identifier

R-HSA-9970191

Type

Reaction [uncertain]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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RBBP6 activates the endonuclease activity of CPSF3, a component of the CPSF complex (Boreikaite et al. 2022; Schmidt et al. 2022). RBBP6 interacts with CPSF3 (Boreikaite et al. 2022; Schmidt et al. 2022) through the DWNN domain of RBBP6 (Schmidt et al. 2022). CPSF3-mediated cleavage of pre-mRNA at a polyadenylation site (PAS) is also stimulated by binding of ATP to CLP1, a subunit of the Cleavage Factor II complex (CF II), but ATP hydrolysis by CLP1 is not required (Schmidt et al. 2022). While Schmidt et al. 2022 reported that the ubiquitin ligase activity of RBBP6 was not required for CPSF3-mediated cleavage of pre-mRNA, Lin et al. 2024 reported that RBBP6-mediated K63-linked ubiquitination of CPSF3 leads to CPSF3 stabilization, resulting in an overall increase of CPSF3 activity.

SUMOylation of CPSF3 and SYMPK (symplekin) has also been reported to affect the activity of the cleavage and polyadenylation complex (CPA) (Vethantham et al. 2007).

Literature References

PubMed ID	Title	Journal	Year
35177537	Reconstitution of 3' end processing of mammalian pre-mRNA reveals a central role of RBBP6 Schmidt, M, Kluge, F, Sandmeir, F, Kühn, U, Schäfer, P, Tüting, C, Ihling, C, Conti, E, Wahle, E	Genes Dev	2022
38503731	RBBP6 maintains glioblastoma stem cells through CPSF3-dependent alternative polyadenylation Lin, P, Chen, W, Long, Z, Yu, J, Yang, J, Xia, Z, Wu, Q, Min, X, Tang, J, Cui, Y, Liu, F, Wang, C, Zheng, J, Li, W, Rich, JN, Li, L, Xie, Q	Cell Discov	2024
35177536	RBBP6 activates the pre-mRNA 3' end processing machinery in humans Boreikaitė, V, Elliott, TS, Chin, JW, Passmore, LA	Genes Dev	2022