Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review
Three-layered control of mRNA poly(A) tail synthesis in Saccharomyces cerevisiae. / Turtola, Matti; Manav, Cemre M.; Kumar, Ananthanarayanan et al.
I: Genes and Development, Bind 35, Nr. 17-18, 09.2021, s. 1290-1303.Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Three-layered control of mRNA poly(A) tail synthesis in Saccharomyces cerevisiae
AU - Turtola, Matti
AU - Manav, Cemre M.
AU - Kumar, Ananthanarayanan
AU - Tudek, Agnieszka
AU - Mroczek, Seweryn
AU - Krawczyk, Pawel S.
AU - Dziembowski, Andrzej
AU - Schmid, Manfred
AU - Passmore, Lori A.
AU - Casanal, Ana
AU - Jensen, Torben Heick
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - Cleavage and polyadenylation factor
KW - MRNA nuclear export
KW - Nab2p
KW - Pab1p
KW - Poly(A) binding protein
KW - Poly(A) tail length
KW - Polyadenylation
UR - http://www.scopus.com/inward/record.url?scp=85115085212&partnerID=8YFLogxK
U2 - 10.1101/GAD.348634.121
DO - 10.1101/GAD.348634.121
M3 - Journal article
C2 - 34385261
AN - SCOPUS:85115085212
VL - 35
SP - 1290
EP - 1303
JO - Genes & Development
JF - Genes & Development
SN - 0890-9369
IS - 17-18
ER -