The goal of the proposed project is to understand the protein composition of ribonucleoprotein complexes containing microRNA miR-29b. MicroRNAs are endogenous, small regulatory RNA molecules. Numerous recent studies have demonstrated that microRNAs are important regulators of gene expression and play crucial roles in a wide range of physiological processes and diseases including cardiovascular and renal diseases. The effect of microRNAs on target genes is mediated by interactions of microRNAs with proteins that, together, form microRNA-containing ribonucleoprotein complexes (miRNPs). Despite the crucial and wide-spread functional role of microRNAs, the number of protein components of miRNPs that have been characterized is surprisingly small. The understanding of proteins interacting with specific microRNAs is particularly lacking, despite the recognition that different microRNAs may act differently. The shortage of knowledge in this critical area significantly hampers in-depth understanding of how microRNAs act, how the action of microRNAs is regulated, and how microRNAs contribute to the regulation of physiology and disease. We propose to develop a new approach for identifying protein components of miRNPs specifically containing miR-29b, a microRNA that we have shown to be functionally important in the protection against hypertensive renal injury.
Aim 1 will develop the approach, identify the protein components, and provide initial characterization of the newly identified proteins.
Aim 2 will examine the functional significance of the newly identified proteins.

Public Health Relevance

The result of the proposed study could significantly improve our understanding of how the action of microRNAs is mediated and enable in-depth studies of how microRNAs contribute to physiological regulation and the development of disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HL111580-02
Application #
8441540
Study Section
Pathobiology of Kidney Disease Study Section (PBKD)
Program Officer
OH, Youngsuk
Project Start
2012-04-01
Project End
2014-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
2
Fiscal Year
2013
Total Cost
$182,070
Indirect Cost
$63,070
Name
Medical College of Wisconsin
Department
Physiology
Type
Schools of Medicine
DUNS #
937639060
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Liu, Yong; Usa, Kristie; Wang, Feng et al. (2018) MicroRNA-214-3p in the Kidney Contributes to the Development of Hypertension. J Am Soc Nephrol 29:2518-2528
Kriegel, Alison J; Terhune, Scott S; Greene, Andrew S et al. (2018) Isomer-specific effect of microRNA miR-29b on nuclear morphology. J Biol Chem 293:14080-14088
Liu, Yong; Liu, Pengyuan; Yang, Chun et al. (2014) Base-resolution maps of 5-methylcytosine and 5-hydroxymethylcytosine in Dahl S rats: effect of salt and genomic sequence. Hypertension 63:827-38
Wang, Feng; Li, Liping; Xu, Haiming et al. (2014) Characteristics of long non-coding RNAs in the Brown Norway rat and alterations in the Dahl salt-sensitive rat. Sci Rep 4:7146
Kriegel, Alison J; Liang, Mingyu (2013) MicroRNA in situ hybridization for formalin fixed kidney tissues. J Vis Exp :
Liang, Mingyu; Cowley Jr, Allen W; Mattson, David L et al. (2013) Epigenomics of hypertension. Semin Nephrol 33:392-9
Jia, Ping; Teng, Jie; Zou, Jianzhou et al. (2013) miR-21 contributes to xenon-conferred amelioration of renal ischemiaýýýreperfusion injury in mice. Anesthesiology 119:621-30
Jia, Ping; Teng, Jie; Zou, Jianzhou et al. (2013) Intermittent exposure to xenon protects against gentamicin-induced nephrotoxicity. PLoS One 8:e64329
Huang, Xiaoyi; Yuan, Tiezheng; Tschannen, Michael et al. (2013) Characterization of human plasma-derived exosomal RNAs by deep sequencing. BMC Genomics 14:319
Jia, Ping; Teng, Jie; Zou, Jianzhou et al. (2013) miR-21 contributes to xenon-conferred amelioration of renal ischemia-reperfusion injury in mice. Anesthesiology 119:621-30

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