TENT5A mediated cytoplasmic polyadenylation in osteoblast supports proper bone formation.
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ABSTRACT: The bone formation, osteogenesis, is a very complex process in which osteoblasts play a crucial role. The primary function of theses terminally differentiated mesenchymal stem cells is the secretion of fibrillary, dense, highly crosslinked type 1 collagen. Herein we show that the TENT5A gene, which mutations lead to osteogenesis imperfecta, is an active cytoplasmic poly(A) polymerase, which in osteoblast positively regulates the expression of collagen subunits and also other secreted proteins essential for proper bone formation. TENT5A substrates have shorter poly(A) tails in TENT5 KO, as revealed by direct RNA sequencing. In the case of Col1α1 and Col1α2 transcripts, the lack of cytoplasmic polyadenylation by TENT5 leads to drastic decree in the protein production but also aberrant structure. The increase in TENT5A expressing during osteoblasts differentiation positively correlates with the cytoplasmic extension of the poly(A) trials of mRNA targets. The first physiologically relevant regulation of collagen expression at the posttranscriptional level.
INSTRUMENT(S): LTQ Orbitrap Velos
ORGANISM(S): Mus Musculus (mouse)
TISSUE(S): Bone
SUBMITTER: Dominik Cysewski
LAB HEAD: Andrzej Dziembowski
PROVIDER: PXD020346 | Pride | 2022-02-16
REPOSITORIES: Pride
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