Department of Neurology; Department of Neurobiology
3' Untranslated Regions; Animals; 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
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.
Rights and Permissions
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.
DOI of Published Version
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 site
Jiao, Jian; Herl, Lauren D.; Farese, Robert V.; and Gao, Fen-Biao, "MicroRNA-29b regulates the expression level of human progranulin, a secreted glycoprotein implicated in frontotemporal dementia" (2010). Neurobiology Publications and Presentations. 18.