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Albrecht, J.C.* ; Reitinger, T.* ; Basquin, J.* ; Schüssler, S.* ; Riggi, M.* ; Schäfer, I.B. ; Conti, E.*

Mechanisms governing poly(A)-tail-length specificity of the human PAN2-PAN3 deadenylase complex.

Cell Rep. 44:116609 (2025)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The lifespan of most eukaryotic mRNAs is modulated by the gradual shortening of the poly(A) tail and removal of the associated poly(A)-binding protein. The human PAN2-PAN3 complex catalyzes initial deadenylation by shortening long poly(A) tails associated with PABPC1. Both PAN2-PAN3 and PABPC1 are evolutionarily conserved from fungi to humans. How the human complex has adapted to recognize and act on longer poly(A) tails characteristic of mammalian mRNAs remains unclear. Here, we report a method to obtain homo-polymeric poly(A) RNAs up to 240 nt, mimicking the synthesis length of poly(A) tails in mammals. We recapitulate human deadenylation properties in vitro, with PAN2-PAN3 showing greater activity on long poly(A)-PABPC1 ribonucleoprotein substrates. Single-particle cryo-electron microscopy (cryo-EM) analyses of PAN2-PAN3 bound to poly(A)-PABPC1 ribonucleoproteins uncover a longer substrate-binding path in the case of the human deadenylase compared to fungi. Altogether, these data provide a rationale for the co-evolution of deadenylase properties and poly(A) tail lengths.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Ccr4-not ; Cp: Molecular Biology ; Pabpc1 ; Pan2-pan3 ; Cryo-em ; Deadenylation ; Mrna Degradation ; Poly(a) Tail ; Ribonucleoproteins; Messenger-rna Deadenylation; Tail Length Control; Cryo-em; Repeating Structure; Binding Proteins; Reveals; Pan2; Refinement; Yeast
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Zeitschrift Cell Reports
Quellenangaben Band: 44, Heft: 12, Seiten: , Artikelnummer: 116609 Supplement: ,
Verlag Cell Press
Verlagsort 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Pancreatic Islet Research (IPI)
Förderungen NOMIS Foundation
Novo Nordisk Foundation ExoAdapt Grant
German Research Foundation
European Research Council
Max Planck Society