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Nuclear RNA decay

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-9930044

PubChem

R-HSA-9930044

Description

In addition to protein coding mRNAs and stable RNAs such as rRNAs, tRNAs, snoRNAs, and snRNAs, the human genome is pervasively transcribed (Clark et al. 2011) to yield other non-coding RNAs such as enhancer transcripts, promoter upstream transcripts (PROMPTs, Preker et al. 2008), long non-coding RNAs (lncRNAs), and apparently non-functional transcripts (reviewed in Ogami and Suzuki 2021). In addition, processing intermediates and abortive transcripts are produced during transcription of mRNAs and stable RNAs. In the nucleus, pervasive unstable transcripts are degraded by nucleases such as the RNA exosome complex (a 3'-5' exonuclease), XRN2 (a 5'-3' exonuclease), and DXO (a 5'-3' exonuclease and a decapping enzyme) (reviewed in Wolin and Maquat 2019, Rambout and Maquat 2024). RNA substrates are directed to the RNA exosome by the nuclear exosome targeting (NEXT) complex, the poly(A) tail exosome targeting (PAXT) connection, and the Trf4/5-Air1/2-Mtr4 polyadenylation (TRAMP) complex. This sorting is crucial to the removal of malformed transcripts and misassembled RNA-protein complexes (reviewed in Wolin and Maquat 2019, Garland and Jensen 2024). Through ZC3H18 or ZC3H4, the NEXT complex (RBM7:ZCCHC8:MTREX) binds capped nonpolyadenylated RNAs (Wu et al. 2020), such as abortive transcripts from RNA polymerase II, recruits the RNA exosome, then the MTREX (MTR4, SKIV2L2) subunit of NEXT unwinds the RNA for introduction into the barrel-shaped RNA exosome (Lubas et al. 2011, Andersen et al. 2013). The PAXT connection (ZFC3H1:MTREX) targets more mature, capped and polyadenylated transcripts (Meola et al. 2016, Wu et al. 2020), and the nucleolar TRAMP complex (MTREX:TENT4A,B:ZCCHC7) targets processing products of rRNA maturation (Sudo et al. 2016). The 5'-3' exonuclease XRN2 is active on RNAs that possess a 5' monophosphate group (inferred from the yeast homolog in Stevens and Poole 1995), but is blocked by a 5' triphosphate or cap structure (reviewed in Miki and Großhans 2013, Nagarajan et al. 2013). Substrates of XRN2 include decapped RNAs and the 3' cleavage products of RNA polymerase II transcripts (reviewed in Miki and Großhans 2013, Nagarajan et al. 2013). The decapping 5'-3 exonuclease DXO can both remove 5' triphosphate or caps (especially unmethylated caps) and exonucleolytically hydrolyze RNAs (Jiao et al. 2013, Doamekpor et al. 2020). DXO is also active on nicotinamide adenine dinucleotide (NAD) cap on RNAs (Jiao et al. 2017) and other "metabolic caps" (several activities and references can be added here, see below). The exonuclease activity of DXO is distributive, while that for XRN2 is processive. The human TRAMP complex is found in a complex with the RNA exosome in the nucleolus where it directs the 5' external transcribed sequence that is cleaved from the 47S pre-rRNA during production of the 45S pre-rRNA (Lubas et al. 2011, Sudo et al. 2016).

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SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying entries **1 - 10** of 21 in total

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UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
O60293	Zinc finger C3H1 domain-containing protein	CCDC131 KIAA0546 PSRC2 ZFC3H1	view
Q01780	Exosome complex component 10	EXOSC10 PMSCL PMSCL2 RRP6	view
Q09161	Nuclear cap-binding protein subunit 1	CBP80 NCBP NCBP1	view
Q13868	Exosome complex component RRP4	EXOSC2 RRP4	view
Q15024	Exosome complex component RRP42	EXOSC7 KIAA0116 RRP42	view
Q5T8P6	RNA-binding protein 26	C13orf10 PRO1777 RBM26	view
Q5XG87	Terminal nucleotidyltransferase 4A	PAPD7 POLS TENT4A TRF4	view
Q6NZY4	Zinc finger CCHC domain-containing protein 8	ZCCHC8	view
Q86U42	Polyadenylate-binding protein 2	PAB2 PABP2 PABPN1	view
Q86VM9	Zinc finger CCCH domain-containing protein 18	NHN1 ZC3H18	view

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