1. Cytoplasmic polyadenylation by TENT5A is required for proper bone formation.
- Author
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Gewartowska O, Aranaz-Novaliches G, Krawczyk PS, Mroczek S, Kusio-Kobiałka M, Tarkowski B, Spoutil F, Benada O, Kofroňová O, Szwedziak P, Cysewski D, Gruchota J, Szpila M, Chlebowski A, Sedlacek R, Prochazka J, and Dziembowski A
- Subjects
- Animals, Cell Differentiation, Collagen Type I genetics, Collagen Type I metabolism, Collagen Type I, alpha 1 Chain genetics, Collagen Type I, alpha 1 Chain metabolism, Disease Models, Animal, Eye Proteins genetics, Eye Proteins metabolism, Female, Gene Expression Regulation, Developmental, Humans, Male, Mice, Mice, Knockout, Nerve Growth Factors genetics, Nerve Growth Factors metabolism, Nucleotidyltransferases genetics, Nucleotidyltransferases metabolism, Osteoblasts pathology, Osteogenesis Imperfecta metabolism, Osteogenesis Imperfecta pathology, Osteonectin genetics, Osteonectin metabolism, Polyadenylation, Polynucleotide Adenylyltransferase metabolism, Protein Isoforms deficiency, Protein Isoforms genetics, RNA, Messenger metabolism, Sequence Analysis, RNA, Serpins genetics, Serpins metabolism, Signal Transduction, Calcification, Physiologic genetics, Osteoblasts metabolism, Osteogenesis genetics, Osteogenesis Imperfecta genetics, Polynucleotide Adenylyltransferase genetics, RNA, Messenger genetics
- Abstract
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 Col1α1, Col1α2, 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 Tent5a 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., Competing Interests: Declaration of interests The authors declare no conflict of interest., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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