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Publication : Cytoplasmic polyadenylation by TENT5A is required for proper bone formation.

First Author  Gewartowska O Year  2021
Journal  Cell Rep Volume  35
Issue  3 Pages  109015
PubMed ID  33882302 Mgi Jnum  J:313854
Mgi Id  MGI:6717031 Doi  10.1016/j.celrep.2021.109015
Citation  Gewartowska O, et al. (2021) Cytoplasmic polyadenylation by TENT5A is required for proper bone formation. Cell Rep 35(3):109015
abstractText  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 Col1alpha1, Col1alpha2, 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.
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