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Cytoplasmic polyadenylation by TENT5A is required for proper bone formation
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SYSNO ASEP 0543446 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Cytoplasmic polyadenylation by TENT5A is required for proper bone formation Author(s) Gewartowska, O. (PL)
Aranaz Novalichez, Goretti (UMG-J)
Krawczyk, P.S. (PL)
Mroczek, S. (PL)
Kusio-Kobialka, M. (PL)
Tarkowski, B. (PL)
Špoutil, František (UMG-J)
Benada, Oldřich (MBU-M) ORCID, RID
Kofroňová, Olga (MBU-M) RID, ORCID
Szwedziak, P. (PL)
Cysewski, D. (PL)
Gruchota, J. (PL)
Szpila, M. (PL)
Chlebowski, A. (PL)
Sedláček, Radislav (UMG-J) RID
Procházka, Jan (UMG-J) ORCID
Dziembowski, A. (PL)Number of authors 17 Article number 109015 Source Title Cell Reports. - : Cell Press - ISSN 2211-1247
Roč. 35, č. 3 (2021)Number of pages 26 s. Publication form Online - E Language eng - English Country US - United States Keywords FAM46A ; Nanopore ; TENT5A ; collagen ; direct RNA sequencing ; osteoblasts ; osteogenesis ; osteogenesis imperfecta ; poly(A) tail ; polyadenylation Subject RIV EB - Genetics ; Molecular Biology OECD category Cell biology R&D Projects LM2015040 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2018126 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) EF16_013/0001789 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED2.1.00/19.0395 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) GJ19-19025Y GA ČR - Czech Science Foundation (CSF) Method of publishing Limited access Institutional support UMG-J - RVO:68378050 ; MBU-M - RVO:61388971 UT WOS 000642161700012 DOI 10.1016/j.celrep.2021.109015 Annotation Osteoblasts orchestrate bone formation through the secretion of type I collagen and other constituents of the matrix on which hydroxyapatite crystals mineralize. Here, we show that TENT5A, whose mutations were found in congenital bone disease osteogenesis imperfecta patients, is a cytoplasmic poly(A) polymerase playing a crucial role in regulating bone mineralization. Direct RNA sequencing revealed that TENT5A is induced during osteoblast differentiation and polyadenylates mRNAs encoding Col1 alpha 1, Col1 alpha 2, and other secreted proteins involved in osteogenesis, increasing their expression. We postulate that TENT5A, possibly together with its paralog TENT5C, is responsible for the wave of cytoplasmic polyadenylation of mRNAs encoding secreted proteins occurring during bone mineralization. Importantly, the Tent5 alpha knockout (KO) mouse line displays bone fragility and skeletal hypomineralization phenotype resulting from quantitative and qualitative collagen defects. Thus, we report a biologically relevant posttranscriptional regulator of collagen production and, more generally, bone formation. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2022 Electronic address https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00329-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124721003296%3Fshowall%3Dtrue
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