title: miR-320a regulates erythroid differentiation through MAR binding protein SMAR1.
abstract: Erythropoiesis is controlled by a complex interplay of several signaling pathways and key transcription factors, as well as microRNAs (miRNAs). MicroRNAs function as critical modulators of gene expression for cellular processes. In the present study, we found that miR-320a inhibits erythroid differentiation by targeting Matrix Attachment Region binding protein SMAR1. miR-320a negatively regulates the expression of SMAR1 by directly binding to its 3'UTR. In response to mild DNA damage, miR-320a expression is decreased resulting in enhanced expression of SMAR1 protein, which in turn, reduces its targets, Bax and Puma inhibiting apoptosis. Our data demonstrate that during hemin-induced erythroid differentiation, enhanced expression of SMAR1 negatively correlates with miR-320a expression. Further analysis reveals that SMAR1 regulates erythroid differentiation, by binding to the promoter of miR-221/222, which play a crucial role in early erythropoiesis. Overall, our studies provide an insight into the regulation of hemin mediated erythroid differentiation of K562 cells through post-transcriptional regulation of SMAR1.
authors.affiliation: Department of Biotechnology, University of Pune, Pune 411007, India; National Centre for Cell Science, Pune University Campus, Ganeshkhind, Pune 411007, India.
authors.forename: Smriti P K
authors.initials: SP
authors.lastname: Mittal
authors.forename: Jinumary
authors.initials: J
authors.lastname: Mathai
authors.forename: Abhijeet P
authors.initials: AP
authors.lastname: Kulkarni
authors.forename: Jayanta K
authors.initials: JK
authors.lastname: Pal
authors.forename: Samit
authors.initials: S
authors.lastname: Chattopadhyay
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D003198:Computer Simulation; D004249:DNA Damage / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D041905:Erythroid Cells / Q000166:cytology* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D045170:Matrix Attachment Regions / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D035683:MicroRNAs; D009687:Nuclear Proteins; D012333:RNA, Messenger; C417914:BANP protein, human; C525709:MIR221, human; C525710:MIR222, human; C572916:MIRN320 microRNA, human
keywords: Erythroid differentiation; Hemin; SMAR1; miR-221/222; miR-320a