Three-layered control of mRNA poly(A) tail synthesis in Saccharomyces cerevisiae
Open Access
- 12 August 2021
- journal article
- research article
- Published by Cold Spring Harbor Laboratory in Journal of Bone and Joint Surgery
- Vol. 35 (17-18), 1290-1303
- https://doi.org/10.1101/gad.348634.121
Abstract
Biogenesis of most eukaryotic mRNAs involves the addition of an untemplated polyadenosine (pA) tail by the cleavage and polyadenylation machinery. The pA tail, and its exact length, impacts mRNA stability, nuclear export, and translation. To define how polyadenylation is controlled in S. cerevisiae, we have used an in vivo assay capable of assessing nuclear pA tail synthesis, analyzed tail length distributions by direct RNA sequencing, and reconstituted polyadenylation reactions with purified components. This revealed three control mechanisms for pA tail length. First, we found that the pA binding protein (PABP) Nab2p is the primary regulator of pA tail length. Second, when Nab2p is limiting, the nuclear pool of Pab1p, the second major PABP in yeast, controls the process. Third, when both PABPs are absent, the cleavage and polyadenylation factor (CPF) limits pA tail synthesis. Thus, Pab1p and CPF provide fail-safe mechanisms to a primary Nab2p-dependent pathway, thereby preventing uncontrolled polyadenylation and allowing mRNA export and translation.Keywords
Funding Information
- Federation of European Biochemical Societies
- EMBO (ALTF 328-2019)
- Novo Nordisk Fonden (NNF19OC0054219)
- Gates Cambridge
- EMBO (ALTF66)
- European Commission (LTFCOFUND2013, GA-2013-609409)
- Marie Curie Actions
- Independent Research Fund Denmark (TEAM/2016-1/3)
- Foundation For Polish Science
- European Research Area Chairs
- European Union (810425)
- European Union's Horizon (725685)
- Medical Research Council
- United Kingdom Research and Innovation (MC_U105192715)
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