Reactome | The PAXT connection (ZFC3H1:MTREX, ZFC3H1:MTR4), RBM26, RBM27, PAPOLG, YTHDC1, and YTHDC2 bind CBCA:polyadenylated m7GpppN-RNA:PABPN1

The PAXT connection (ZFC3H1:MTREX, ZFC3H1:MTR4), RBM26, RBM27, PAPOLG, YTHDC1, and YTHDC2 bind CBCA:polyadenylated m7GpppN-RNA:PABPN1

Stable Identifier

R-HSA-9933559

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

Locations in the PathwayBrowser

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The PAXT connection (ZFC3H1:MTREX, ZFC3H1:MTR4), RBM26, RBM27, PAPOLG, YTHDC1, and YTHDC2 bind CBCA:polyadenylated m7GpppN-RNA:PABPN1

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During RNA transcription, ZFC3H1 binds the first exon and first intron of nascent RNAs (Fan et al. 2024). On short RNAs with few exons (Fan et al. 2024) ZFC3H1 then binds MTREX (MTR4, SKIV2L2), forming the PAXT connection: ZFC3H1:MTREX (Meola et al. 2016, Fan et al. 2024). ZFC3H1 of the PAXT connection binds ARS2 (SRRT) of the cap binding complex CBCA (Meola et al. 2016, Polak et al. 2023) and the binding is mostly RNA-sensitive (Meola et al. 2016). ZFC3H1 also interacts with PABPN1 bound to the polyadenylate tail of the RNA, thus PAXT is targeted to capped, polyadenylated RNAs (Meola et al. 2016). ZFC3H1 of PAXT and ZC3H18 associated with the NEXT complex compete for binding to the ARS2 (SRRT) subunit of the CBCA complex (Polak et al. 2023), determining whether the RNA will be degraded by the PAXT-dependent pathway or the NEXT-dependent pathway.
ZC3H3 directly interacts with the PAXT connection independently of RNA. (Silla et al. 2020). Both RBM27 and its paralog RBM26 are present in the larger PAXT:PARN2:ZC3H3 complex and participate in PAXT-dependent RNA decay (Silla et al. 2020, Contreras et al. 2023). The polyadenylate polymerase PAPOLG (PAPgamma) interacts with ZFC3H1 of the PAXT connection and appears to participate in 3' polyadenylation of promoter upstream transcripts (PROMPTs) (Contreras et al. 2023). As judged by coimmunoprecipitation, the 6-methyladenosine readers YTHDC1 and YTHDC2 also associate with ZFC3H1 (Contreras et al. 2023). The overall subunit composition of the larger PAXT complex resembles the MTREC complex of yeast (Contreras et al. 2023).

Literature References

PubMed ID	Title	Journal	Year
27871484	Identification of a Nuclear Exosome Decay Pathway for Processed Transcripts Meola, N, Domanski, M, Karadoulama, E, Chen, Y, Gentil, C, Pultz, D, Vitting-Seerup, K, Lykke-Andersen, S, Andersen, JS, Sandelin, A, Jensen, TH	Mol Cell	2016
37875486	PAPγ associates with PAXT nuclear exosome to control the abundance of PROMPT ncRNAs Contreras, X, Depierre, D, Akkawi, C, Srbic, M, Helsmoortel, M, Nogaret, M, LeHars, M, Salifou, K, Heurteau, A, Cuvier, O, Kiernan, R	Nat Commun	2023
39461342	Dual modes of ZFC3H1 confer selectivity in nuclear RNA sorting Fan, J, Wang, Y, Wen, M, Tong, D, Wu, K, Yan, K, Jia, P, Zhu, Y, Liu, Q, Zou, H, Zhao, P, Lu, F, Yun, C, Xue, Y, Zhou, Y, Cheng, H	Mol Cell	2024
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
31950173	The human ZC3H3 and RBM26/27 proteins are critical for PAXT-mediated nuclear RNA decay Silla, T, Schmid, M, Dou, Y, Garland, W, Milek, M, Imami, K, Johnsen, D, Polak, P, Andersen, JS, Selbach, M, Landthaler, M, Jensen, TH	Nucleic Acids Res	2020