title: Mammalian PNLDC1 is a novel poly(A) specific exonuclease with discrete expression during early development.
abstract: PNLDC1 is a homologue of poly(A) specific ribonuclease (PARN), a known deadenylase with additional role in processing of non-coding RNAs. Both enzymes were reported recently to participate in piRNA biogenesis in silkworm and C. elegans, respectively. To get insights on the role of mammalian PNLDC1, we characterized the human and mouse enzymes. PNLDC1 shows limited conservation compared to PARN and represents an evolutionary related but distinct group of enzymes. It is expressed specifically in mouse embryonic stem cells, human and mouse testes and during early mouse embryo development, while it fades during differentiation. Its expression in differentiated cells, is suppressed through methylation of its promoter by the de novo methyltransferase DNMT3B. Both enzymes are localized mainly in the ER and exhibit in vitro specificity restricted solely to 3' RNA or DNA polyadenylates. Knockdown of Pnldc1 in mESCs and subsequent NGS analysis showed that although the expression of the remaining deadenylases remains unaffected, it affects genes involved mainly in reprogramming, cell cycle and translational regulation. Mammalian PNLDC1 is a novel deadenylase expressed specifically in cell types which share regulatory mechanisms required for multipotency maintenance. Moreover, it could be involved both in posttranscriptional regulation through deadenylation and genome surveillance during early development.
authors: Department of Biochemistry, School of Medicine, University of Patras, 26504 Rio Achaia, Greece.
authors: Dimitrios
authors: D
authors: Anastasakis
authors: Department of Biochemistry, School of Medicine, University of Patras, 26504 Rio Achaia, Greece.
authors: Ilias
authors: I
authors: Skeparnias
authors: Department of Biochemistry, School of Medicine, University of Patras, 26504 Rio Achaia, Greece.
authors: Athanasios-Nasir
authors: AN
authors: Shaukat
authors: Department of Biochemistry, School of Medicine, University of Patras, 26504 Rio Achaia, Greece.
authors: Katerina
authors: K
authors: Grafanaki
authors: Department of Physiology, School of Medicine, University of Patras, 26504 Rio Achaia, Greece.
authors: Alexandra
authors: A
authors: Kanellou
authors: Department of Physiology, School of Medicine, University of Patras, 26504 Rio Achaia, Greece.
authors: Stavros
authors: S
authors: Taraviras
authors: Department of Anatomy, Histology and Embryology, School of Medicine, University of Patras, 26504 Rio Achaia, Greece.
authors: Dionysios J
authors: DJ
authors: Papachristou
authors: Laboratory of Chemical Biology, National Centre for Scientific Research 'Demokritos', 15341 Athens, Greece.
authors: Athanasios
authors: A
authors: Papakyriakou
authors: Department of Biochemistry, School of Medicine, University of Patras, 26504 Rio Achaia, Greece cstath@med.upatras.gr.
authors: Constantinos
authors: C
authors: Stathopoulos
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D047108:Embryonic Development / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005095:Exoribonucleases / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008745:Methylation; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D011061:Poly A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D026723:Polyadenylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport
chemical_list: D005095:Exoribonucleases; D011061:Poly A