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.
- Klíčová slova
- FAM46A, Nanopore, TENT5A, collagen, direct RNA sequencing, osteoblasts, osteogenesis, osteogenesis imperfecta, poly(A) tail, polyadenylation,
- MeSH
- buněčná diferenciace MeSH
- fyziologická kalcifikace genetika MeSH
- kolagen typu I, řetězec alfa 1 genetika metabolismus MeSH
- kolagen typu I genetika metabolismus MeSH
- lidé MeSH
- messenger RNA genetika metabolismus MeSH
- modely nemocí na zvířatech MeSH
- myši knockoutované MeSH
- myši MeSH
- neurotrofní faktory genetika metabolismus MeSH
- nukleotidyltransferasy genetika metabolismus MeSH
- oční proteiny genetika metabolismus MeSH
- osteoblasty metabolismus patologie MeSH
- osteogenesis imperfecta genetika metabolismus patologie MeSH
- osteogeneze genetika MeSH
- osteonektin genetika metabolismus MeSH
- poly(A)-polymerasa genetika metabolismus MeSH
- polyadenylace MeSH
- protein - isoformy nedostatek genetika MeSH
- sekvenční analýza RNA MeSH
- serpiny genetika metabolismus MeSH
- signální transdukce MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- Col1a1 protein, mouse MeSH Prohlížeč
- Col1a2 protein, mouse MeSH Prohlížeč
- kolagen typu I, řetězec alfa 1 MeSH
- kolagen typu I MeSH
- messenger RNA MeSH
- neurotrofní faktory MeSH
- nukleotidyltransferasy MeSH
- oční proteiny MeSH
- osteonektin MeSH
- pigment epithelium-derived factor MeSH Prohlížeč
- poly(A)-polymerasa MeSH
- protein - isoformy MeSH
- serpiny MeSH
- SPARC protein, mouse MeSH Prohlížeč
- TENT5A protein, human MeSH Prohlížeč
- Tent5A protein, mouse MeSH Prohlížeč
- Tent5c protein, mouse MeSH Prohlížeč
