MicroRNA-29b regulates the expression level of human progranulin, a secreted glycoprotein implicated in frontotemporal dementia
Document Type
Journal ArticlePublication Date
2010-05-10Keywords
3' Untranslated RegionsAnimals
Base Sequence
Binding Sites
Cell Line
Frontotemporal Dementia
*Gene Expression Regulation
Gene Knockdown Techniques
Genes, Reporter
Glycoproteins
Humans
Intercellular Signaling Peptides and
Proteins
Intracellular Space
Luciferases
Mice
MicroRNAs
Molecular Sequence Data
NIH 3T3 Cells
Protein Binding
RNA, Messenger
Neuroscience and Neurobiology
Metadata
Show full item recordAbstract
Progranulin deficiency is thought to cause some forms of frontotemporal dementia (FTD), a major early-onset age-dependent neurodegenerative disease. How progranulin (PGRN) expression is regulated is largely unknown. We identified an evolutionarily conserved binding site for microRNA-29b (miR-29b) in the 3' untranslated region (3'UTR) of the human PGRN (hPGRN) mRNA. miR-29b downregulates the expression of luciferase through hPGRN or mouse PGRN (mPGRN) 3'UTRs, and the regulation was abolished by mutations in the miR-29b binding site. To examine the direct effect of manipulating endogenous miR-29b on hPGRN expression, we established a stable NIH3T3 cell line that expresses hPGRN under the control of the cytomegalovirus promoter. Ectopic expression of miR-29b decreased hPGRN expression at the both mRNA and protein levels. Conversely, knockdown of endogenous miR-29b with locked nucleic acid increased the production and secretion of hPGRN in NIH3T3 cells. Endogenous hPGRN in HEK 293 cells was also regulated by miR-29b. These findings identify miR-29b as a novel posttranscriptional regulator of PGRN expression, raising the possibility that miR-29b or other miRNAs might be targeted therapeutically to increase hPGRN levels in some FTD patients.Source
Jiao J, Herl LD, Farese RV Jr, Gao F-B (2010) MicroRNA-29b Regulates the Expression Level of Human Progranulin, a Secreted Glycoprotein Implicated in Frontotemporal Dementia. PLoS ONE 5(5): e10551. doi:10.1371/journal.pone.0010551. Link to article on publisher's siteDOI
10.1371/journal.pone.0010551Permanent Link to this Item
http://hdl.handle.net/20.500.14038/37909PubMed ID
20479936Related Resources
Link to Article in PubMedRights
Copyright: © 2010 Jiao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0010551