Reactome | The NEXT complex binds ZC3H4:WDR82:CBCA:m7GpppN-RNA

The NEXT complex binds ZC3H4:WDR82:CBCA:m7GpppN-RNA

Stable Identifier

R-HSA-9930059

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

3/5

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The NEXT complex binds ZC3H4:WDR82:CBCA:m7GpppN-RNA

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The ZC3H4:WDR82 complex (Austenaa et al. 2021, Estell et al. 2023) binds capped RNAs via an interaction between ZC3H4 and SRRT (ARS2) of the CBCA complex (CBP80:CBP20:ARS2, also called NCBP1:NCBP2:SRRT) at the 5' cap of the RNA (Rouvière et al. 2023, Estell et al. 2023). ZC3H4 also binds a homodimer of the NEXT complex (RBM7:ZCCHC8:MTREX, MTREX is also known as SKIV2L2 and MTR4) (Puno and Lima 2022, Gerlach et al. 2022), which interacts with the RNA exosome to degrade RNA (Rouvière et al. 2023, Estell et al. 2023).
ZC3H4 appears to target capped RNAs produced from transcripts that are terminated by the Terminator complex (ZC3H4:WDR82:SRRT) (Estell et al. 2023, reviewed in Rambout and Maquat 2024). Transcripts regulated by ZC3H4 include inefficiently spliced non-coding RNAs (Austemaa et al. 2021), antisense RNAs (Estell et al. 2021), and transcripts from enhancers (Estell et al. 2021). 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).

Literature References

PubMed ID	Title	Journal	Year
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
37329883	A restrictor complex of ZC3H4, WDR82, and ARS2 integrates with PNUTS to control unproductive transcription Estell, C, Davidson, L, Eaton, JD, Kimura, H, Gold, VAM, West, S	Mol Cell	2023
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
33913806	ZC3H4 restricts non-coding transcription in human cells Estell, C, Davidson, L, Steketee, PC, Monier, A, West, S	Elife	2021
37329882	ARS2 instructs early transcription termination-coupled RNA decay by recruiting ZC3H4 to nascent transcripts Rouvière, JO, Salerno-Kochan, A, Lykke-Andersen, S, Garland, W, Dou, Y, Rathore, O, Molska, EŠ, Wu, G, Schmid, M, Bugai, A, Jakobsen, L, Žumer, K, Cramer, P, Andersen, JS, Conti, E, Jensen, TH	Mol Cell	2023
35688134	Structural basis for RNA surveillance by the human nuclear exosome targeting (NEXT) complex Puno, MR, Lima, CD	Cell	2022
33767452	A first exon termination checkpoint preferentially suppresses extragenic transcription Austenaa, LMI, Piccolo, V, Russo, M, Prosperini, E, Polletti, S, Polizzese, D, Ghisletti, S, Barozzi, I, Diaferia, GR, Natoli, G	Nat Struct Mol Biol	2021