Abstract
Osteoblasts orchestrate bone formation through the secretion of collagen type I and other constituents of the matrix on which hydroxyapatite crystals mineralize. Here we show that cytoplasmic poly(A) polymerase, TENT5A, whose mutations were found in osteogenesis imperfecta patients, plays 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 is responsible for the wave of cytoplasmic polyadenylation of mRNAs encoding secreted proteins occurring during bone mineralization. Importantly, the TENT5A KO mouse line displays bone fragility and skeletal hypomineralization phenotype resulting from quantitative and qualitative collagen defects. Thus, for the first time, we report a biologically relevant posttranscriptional regulator of collagen production and, more generally, bone formation.
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