A Novel Nuclear Human Poly(A) Polymerase (PAP), PAPγ

Kyriakopoulou, Christina; Nordvarg, Helena; Virtanen, Anders

doi:10.1074/jbc.m104599200

Cited by 58 publications

(64 citation statements)

References 51 publications

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“…The structures of human, bovine and yeast PAP have been reported [182][183][184][185]. Overall, the structure of PAP contains three domains, N-terminal, middle and C-terminal domains (Fig.…”

Section: Poly(a) Polymerase (Pap1p)mentioning

confidence: 99%

Protein factors in pre-mRNA 3′-end processing

Mandel

Bai

Tong

2007

Cell. Mol. Life Sci.

365

482

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Most eukaryotic mRNA precursors (pre-mRNAs) must undergo extensive processing, including cleavage and polyadenylation at the 3′-end. Processing at the 3′-end is controlled by sequence elements in the pre-mRNA (cis elements) as well as protein factors. Despite the seeming biochemical simplicity of the processing reactions, more than 14 proteins have been identified for the mammalian complex, and more than 20 proteins have been identified for the yeast complex. The 3′-end processing machinery also has important roles in transcription and splicing. The mammalian machinery contains several sub-complexes, including cleavage and polyadenylation specificity factor (CPSF), cleavage stimulation factor (CstF), cleavage factor I (CF I m ), and cleavage factor II (CF II m ). Additional protein factors include poly(A) polymerase (PAP), poly(A) binding protein (PABP), symplekin, and the C-terminal domain (CTD) of RNA polymerase II largest subunit. The yeast machinery includes cleavage factor IA (CF IA), cleavage factor IB (CF IB), and cleavage and polyadenylation factor (CPF).

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Section: Poly(a) Polymerase (Pap1p)mentioning

confidence: 99%

Protein factors in pre-mRNA 3′-end processing

Mandel

Bai

Tong

2007

Cell. Mol. Life Sci.

365

482

View full text Add to dashboard Cite

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Section: Downloaded Frommentioning

confidence: 99%

“…First, this isoform is known to function in a mechanism that depends on both cleavage-polyadenylation specificity factor and the AAUAAA polyadenylation signal (34). Second, highquality anti-PAP-␥ is available (34). Protein was isolated before or after IP using nuclear extracts from untransfected HeLa CCL2 cells and rabbit polyclonal anti-PAP-␥ or, as a negative control, NRS.…”

Section: Downloaded Frommentioning

confidence: 99%

Evidence that Poly(A) Binding Protein C1 Binds Nuclear Pre-mRNA Poly(A) Tails

Hosoda

Lejeune

Maquat

2006

Molecular and Cellular Biology

103

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In mammalian cells, poly(A) binding protein C1 (PABP C1) has well-known roles in mRNA translation and decay in the cytoplasm. However, PABPC1 also shuttles in and out of the nucleus, and its nuclear function is unknown. Here, we show that PABPC1, like the major nuclear poly(A) binding protein PABPN1, associates with nuclear pre-mRNAs that are polyadenylated and intron containing. PABPC1 does not bind nonpolyadenylated histone mRNA, indicating that the interaction of PABPC1 with pre-mRNA requires a poly(A) tail. Consistent with this conclusion, UV cross-linking results obtained using intact cells reveal that PABPC1 binds directly to pre-mRNA poly(A) tails in vivo. We also show that PABPC1 immunopurifies with poly(A) polymerase, suggesting that PABPC1 is acquired by polyadenylated transcripts during poly(A) tail synthesis. Our findings demonstrate that PABPC1 associates with polyadenylated transcripts earlier in mammalian mRNA biogenesis than previously thought and offer insights into the mechanism by which PABPC1 is recruited to newly synthesized poly(A). Our results are discussed in the context of pre-mRNA processing and stability and mRNA trafficking and the pioneer round of translation.The 3Ј ends of almost all eukaryotic mRNAs and their precursors consist of homopolymeric tails of adenosine, or poly(A), that are added by poly(A) polymerase (PAP) during the process of 3Ј end formation. There are two classes of poly(A) binding proteins (PABPs) in mammalian cells (32,40). One class is exemplified by PABPN1, formerly called PABP2. PABPN1 is primarily nuclear and plays a role in the synthesis of poly(A) tails, but it also shuttles between the nucleus and cytoplasm (5,8,9,31,53). The other class consists of the primarily cytoplasmic PABPs, of which PABPC1, formerly called PABI or PABP1, is the major form in mammalian somatic cells (40). In humans, at least four separate PABPC genes and four pseudogenes have been identified (40). PABPC1 influences mRNA translation and decay (18,20,23,27,29,30,50,(54)(55)(56), and it shuttles between the nucleus and cytoplasm of at least some mammalian cells (1,57,58). Consistent with the preferential compartmentalization of PABPN1 to the nucleus and PABPC1 to the cytoplasm, a physical interaction has been detected between PAP and PABPN1 but not PABPC1 (28). Furthermore, PABPN1 associates with RNA polymerase II during transcription and accompanies the released transcript to the nuclear pore (2). Given that PABPC1 can exist within nuclei, a key issue is whether PABPC1 binds to transcripts inside the nucleus, and if it does, at which step in mRNA maturation.The 5Ј ends of eukaryotic mRNAs and their precursors are capped, and the cap is initially bound by the mostly nuclear cap binding protein (CBP) heterodimer of CBP80 and CBP20 (25, 35, 38), which will be called CBP80/CBP20. CBP80/CBP20 is detectably replaced by the mostly cytoplasmic eukaryotic translation initiation factor 4E (eIF4E) only after introns have been removed by splicing (35). Evidence indicates that PABPC1 is a component...

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“…5). Canonical PAPs, which include nuclear and cytoplasmic enzymes, are all closely related [12][13][14][15] ; they are monomeric and possess three key domains (Fig. 5, left) 8,9 .…”

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confidence: 99%