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Cytoplasmic polyadenylation by TENT5A is required for proper bone formation

cris.lastimport.scopus2024-02-12T20:49:46Z
dc.abstract.enOsteoblasts 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.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorKusio-Kobiałka, Monika
dc.contributor.authorSzwedziak, Piotr
dc.contributor.authorKofroňová, Olga
dc.contributor.authorBenada, Oldrich
dc.contributor.authorTarkowski, Bartosz
dc.contributor.authorProchazka, Jan
dc.contributor.authorDziembowski, Andrzej
dc.contributor.authorSedlacek, Radislav
dc.contributor.authorMROCZEK, SEWERYN
dc.contributor.authorChlebowski, Aleksander
dc.contributor.authorKrawczyk, Paweł
dc.contributor.authorCysewski, Dominik
dc.contributor.authorGewartowska, Olga
dc.contributor.authorSpoutil, Frantisek
dc.contributor.authorAranaz-Novaliches, Goretti
dc.contributor.authorGRUCHOTA, JAKUB
dc.contributor.authorSzpila, Marcin
dc.date.accessioned2024-01-24T21:15:28Z
dc.date.available2024-01-24T21:15:28Z
dc.date.copyright2021-04-20
dc.date.issued2021
dc.description.accesstimeAT_PUBLICATION
dc.description.financePublikacja bezkosztowa
dc.description.number3
dc.description.versionFINAL_PUBLISHED
dc.description.volume35
dc.identifier.doi10.1016/J.CELREP.2021.109015
dc.identifier.issn2211-1247
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/104097
dc.identifier.weblinkhttps://api.elsevier.com/content/article/PII:S2211124721003296?httpAccept=text/xml
dc.languageeng
dc.pbn.affiliationbiological sciences
dc.relation.ispartofCell Reports
dc.relation.pages109015
dc.rightsCC-BY-NC-ND
dc.sciencecloudnosend
dc.subject.enTENT5A
dc.subject.enFAM46A
dc.subject.enosteogenesis
dc.subject.enosteogenesis imperfecta
dc.subject.enpolyadenylation osteoblasts
dc.subject.endirect RNA sequencing
dc.subject.encollagen
dc.subject.enNanopore
dc.subject.enpoly(A) tail
dc.titleCytoplasmic polyadenylation by TENT5A is required for proper bone formation
dc.typeJournalArticle
dspace.entity.typePublication