Reactome | The NEXT complex and ZC3H18 bind CBCA:m7GpppN-RNA

The NEXT complex and ZC3H18 bind CBCA:m7GpppN-RNA

Stable Identifier

R-HSA-9930056

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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The NEXT complex and ZC3H18 bind CBCA:m7GpppN-RNA

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The CBCA complex (CBP80:CBP20:ARS2, also called NCBP1:NCBP2:SRRT) is bound to the m7GpppN cap of an RNA. ZC3H18 interacts with the SRRT (ARS2) subunit of the CBCA complex (Winczura et al. 2018, Polák et al. 2023) and the NEXT complex (RBM7:ZCCHC8:MTREX) (Lubas et al. 2011, Winczura et al. 2018) to form the CBCN complex (Andersen et al. 2013). The NEXT complex binds lower amounts of RNA exosome components than CBCA components suggesting that some portion of the CBCN complex is not bound to the RNA exosome (Andersen et al. 2013).
The NEXT complex binds ZC3H18 as a homodimer and all subunits of the NEXT complex participate in interaction with RNA (Puno and Lima 2022, Gerlach et al. 2022). Substrate RNAs of NEXT are generally not polyadenylated, do not have polyadenylation sequences (Wu et al. 2020), and include promoter upstream transcripts (PROMPTS) and enhancer RNAs (eRNAs) (Lubas et al. 2015). ZC3H18 is believed to initiate degradation of RNAs that are produced from paused transcripts released from transcription complexes by the endonucleolytic activity of the Integrator complex (reviewed in Rambout and Maquat 2024). ZC3H18, which interacts with the NEXT complex, and ZC3H1, which interacts with the PAXT connection, compete for binding to the same site on SRRT (ARS2) (Polák et al. 2023). The PAXT connection may thus compete with the NEXT complex for substrate RNAs and may act as a fail-safe system for RNAs that escape targeting by NEXT (Wu et al. 2020)

Literature References

PubMed ID	Title	Journal	Year
21855801	Interaction profiling identifies the human nuclear exosome targeting complex Lubas, M, Christensen, MS, Kristiansen, MS, Domanski, M, Falkenby, LG, Lykke-Andersen, S, Andersen, JS, Dziembowski, A, Jensen, TH	Mol. Cell	2011
32075771	A Two-Layered Targeting Mechanism Underlies Nuclear RNA Sorting by the Human Exosome Wu, G, Schmid, M, Rib, L, Polak, P, Meola, N, Sandelin, A, Jensen, TH	Cell Rep	2020
35688157	Structure and regulation of the nuclear exosome targeting complex guides RNA substrates to the exosome Gerlach, P, Garland, W, Lingaraju, M, Salerno-Kochan, A, Bonneau, F, Basquin, J, Jensen, TH, Conti, E	Mol Cell	2022
25578728	The human nuclear exosome targeting complex is loaded onto newly synthesized RNA to direct early ribonucleolysis Lubas, M, Andersen, PR, Schein, A, Dziembowski, A, Kudla, G, Jensen, TH	Cell Rep	2015
37889751	Dual agonistic and antagonistic roles of ZC3H18 provide for co-activation of distinct nuclear RNA decay pathways Polák, P, Garland, W, Rathore, O, Schmid, M, Salerno-Kochan, A, Jakobsen, L, Gockert, M, Gerlach, P, Silla, T, Andersen, JS, Conti, E, Jensen, TH	Cell Rep	2023
24270879	The human cap-binding complex is functionally connected to the nuclear RNA exosome Andersen, PR, Domanski, M, Kristiansen, MS, Storvall, H, Ntini, E, Verheggen, C, Schein, A, Bunkenborg, J, Poser, I, Hallais, M, Sandberg, R, Hyman, A, LaCava, J, Rout, MP, Andersen, JS, Bertrand, E, Jensen, TH	Nat Struct Mol Biol	2013
35688134	Structural basis for RNA surveillance by the human nuclear exosome targeting (NEXT) complex Puno, MR, Lima, CD	Cell	2022
29298432	Characterizing ZC3H18, a Multi-domain Protein at the Interface of RNA Production and Destruction Decisions Winczura, K, Schmid, M, Iasillo, C, Molloy, KR, Harder, LM, Andersen, JS, LaCava, J, Jensen, TH	Cell Rep	2018