Transcript shortening via alternative polyadenylation promotes gene expression during fracture healing

作     者：Deepak Kumar Khajuria Irena Nowak Ming Leung Vengadeshprabhu Karuppagounder Yuka Imamura Christopher C.Norbury Fadia Kamal Reyad A.Elbarbary Deepak Kumar Khajuria;Irena Nowak;Ming Leung;Vengadeshprabhu Karuppagounder;Yuka Imamura;Christopher C.Norbury;Fadia Kamal;Reyad A.Elbarbary

作者机构：Department of Orthopaedics and RehabilitationThe Pennsylvania State University College of MedicineHersheyPA17033USA Center for Orthopaedic Research and Translational Science(CORTS)The Pennsylvania State University College of MedicineHersheyPA17033USA Institute for Personalized MedicinePenn State College of MedicineHersheyPA17033USA Department of PharmacologyThe Pennsylvania State University College of MedicineHersheyPA17033USA Department of Microbiology and ImmunologyThe Pennsylvania State University College of MedicineHersheyPA17033USA Department of Biochemistry and Molecular BiologyThe Pennsylvania State University College of MedicineHersheyPA17033USA Center for RNA Molecular BiologyPennsylvania State UniversityUniversity ParkPA16802USA 

出 版 物：《Bone Research》 (骨研究（英文版）)

年 卷 期：2023年第11卷第1期

页      面：163-177页

核心收录：

学科分类：1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

基　　金：National Institutes of Health(NIH)R01 DK121327 to R.A.E 

主　　题：healing metabolism shortening 

摘      要：Maturation of the 3′end of almost all eukaryotic messenger RNAs(m RNAs)requires cleavage and *** mammalian m RNAs are polyadenylated at different sites within the last exon,generating alternative polyadenylation(APA)isoforms that have the same coding region but distinct 3′untranslated regions(UTRs).The 3′UTR contains motifs that regulate m RNA metabolism;thus,changing the 3′UTR length via APA can significantly affect gene *** ossification is a central process in bone healing,but the impact of APA on gene expression during this process is ***,we report the widespread occurrence of APA,which impacts multiple pathways that are known to participate in bone ***,the progression of endochondral ossification involves global 3′UTR shortening,which is coupled with an increased abundance of shortened transcripts relative to other transcripts;these results highlight the role of APA in promoting gene expression during endochondral bone *** mechanistic studies of transcripts that undergo APA in the fracture callus revealed an intricate regulatory network in which APA enhances the expression of the collagen,type I,alpha 1(Col1a1)and Col1a2 genes,which encode the 2 subunits of the abundantly expressed protein collagen *** exerts this effect by shortening the 3′UTRs of the Col1a1 and Col1a2 m RNAs,thus removing the binding sites of mi R-29a-3p,which would otherwise strongly promote the degradation of both *** together,our study is the first to characterize the crucial roles of APA in regulating the 3′UTR landscape and modulating gene expression during fracture healing.