Dual agonistic and antagonistic roles of ZC3H18 provide for co-activation of distinct nuclear RNA decay pathways

Polák, Patrik; Garland, William; Rathore, Om; Schmid, Manfred; Salerno-Kochan, Anna; Jakobsen, Lis; Gockert, Maria; Gerlach, Piotr; Silla, Toomas; Andersen, Jens S.; Conti, Elena; Jensen, Torben Heick

doi:10.1016/j.celrep.2023.113325

Cited by 3 publications

(2 citation statements)

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“…Conventional 3’end polyadenylation by the cleavage and polyadenylation (CPA) complex largely occurs co-transcriptionally and is critical for further RNA processing, stability, nuclear export and translation 96–99 . In a countering destructive pathway, the RNA polyA tail and its nuclear pA-binding protein (PABPN1) can direct transcripts for decay by the PAXT/exosome pathway 30–32,36,39,40,100–103 . Additionally, short polyA tails, added by the mammalian Trf4/Air2/Mtr4 polyadenylation (TRAMP) complex promote the turnover of rRNA processing byproducts through the nuclear exosome 30,104 .…”

Section: Discussionmentioning

confidence: 99%

“…NEXT forms a dimer of MTR4-ZCCHC8-RBM7 heterotrimers 33,34 and can target the exosome to short, TSS-proximal, pA - transcripts via its connection to the 5’cap-binding complex (CBC) 35–37 . Conversely, PAXT consists of a core MTR4-ZFC3H1 heterodimer, that associates with the nuclear pA binding protein (PABPN1) to facilitate the exosome-mediated decay of a variety of pA + RNAs 31,32,38–40 . By their combined targeting of pA - and pA + RNAs, NEXT and PAXT are believed to provide for much of the nuclear control of RNAPII-derived transcripts.…”

Section: Introductionmentioning

confidence: 99%

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RNA 3’end tailing safeguards cells against products of pervasive transcription termination

Wu,

Rouvière,

Schmid

et al. 2024

Preprint

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Premature transcription termination yields a wealth of unadenylated (pA-) RNA. Although this can be targeted for degradation by the Nuclear EXosome Targeting (NEXT) complex, possible back-up pathways remain poorly understood. Here, we find RNA 3′ end uridylation and adenylation upon NEXT inactivation. U-tailed RNAs are generally short and modified by the cytoplasmic tailing enzymes, TUT4/7, following their PHAX-dependent nuclear export and prior to their degradation by the cytoplasmic exosome or the exoribonuclease DIS3L2. Longer RNAs are instead adenylated redundantly by enzymes TENT2, PAPOLA and PAPOLG. These transcripts are either degraded via the nuclear Poly(A) tail eXosome Targeting (PAXT) connection or exported by conventional factors and removed by the cytoplasmic exosome in a translation-dependent manner. Failure to do so decreases global translation and induces cell death. We conclude that post-transcriptional 3′ end modification and removal of excess pA- RNA is achieved by tailing enzymes and export factors shared with productive RNA pathways.

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