Cytoplasmic polyadenylation by TENT5A is required for proper bone formation

0543446 - ÚMG 2022 RIV US eng J - Journal Article
Gewartowska, O. - Aranaz Novalichez, Goretti - Krawczyk, P.S. - Mroczek, S. - Kusio-Kobialka, M. - Tarkowski, B. - Špoutil, František - Benada, Oldřich - Kofroňová, Olga - Szwedziak, P. - Cysewski, D. - Gruchota, J. - Szpila, M. - Chlebowski, A. - Sedláček, Radislav - Procházka, Jan - Dziembowski, A.
Cytoplasmic polyadenylation by TENT5A is required for proper bone formation.
Cell Reports. Roč. 35, č. 3 (2021), č. článku 109015. ISSN 2211-1247. E-ISSN 2211-1247
R&D Projects: GA MŠMT(CZ) LM2015040; GA MŠMT(CZ) LM2018126; GA MŠMT EF16_013/0001789; GA MŠMT ED2.1.00/19.0395; GA MŠMT(CZ) ED1.1.00/02.0109; GA ČR GJ19-19025Y
Institutional support: RVO:68378050 ; RVO:61388971
Keywords : FAM46A * Nanopore * TENT5A * collagen * direct RNA sequencing * osteoblasts * osteogenesis * osteogenesis imperfecta * poly(A) tail * polyadenylation
OECD category: Cell biology; Cell biology (MBU-M)
Impact factor: 9.995, year: 2021
Method of publishing: Limited access
https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00329-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124721003296%3Fshowall%3Dtrue

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.
Permanent Link: http://hdl.handle.net/11104/0320651