Atherosclerosis is a pathogenic consequence of uncontrolled inflammation of the resident cells of vessel wall. Using cell-based model we showed that ribosomal protein L13a-dependent translational silencing pathway could terminate the expression of a group of inflammatory genes. In this proposal we will test whether this mechanism can resolve inflammation. We have demonstrated that IFN-3 induced synthesis of Ceruloplasmin (Cp) and a group of other inflammatory proteins in monocytic cells is under translational control. Further, we discovered a crucial role of ribosomal protein L13a and its release from 60S ribosome in the formation of IFN- Gamma-Activated Inhibitor of Translation (GAIT) complex. The translational silencing mechanism relies on the recognition of L13a-dependent GAIT complex by the GAIT element present in the 3

Public Health Relevance

Uncontrolled inflammation is the cause of many diseases such as atherosclerosis or cardiovascular disease. This research will uncover the insight about the endogenous cellular mechanisms to control the expression of inflammatory molecules and help to generate novel therapeutic agents against inflammatory diseases.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL079164-09
Application #
8457084
Study Section
Atherosclerosis and Inflammation of the Cardiovascular System Study Section (AICS)
Program Officer
Srinivas, Pothur R
Project Start
2005-03-01
Project End
2015-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
9
Fiscal Year
2013
Total Cost
$318,559
Indirect Cost
$94,222
Name
Cleveland State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
010841617
City
Cleveland
State
OH
Country
United States
Zip Code
44115
Basu, Abhijit; Poddar, Darshana; Robinet, Peggy et al. (2014) Ribosomal protein L13a deficiency in macrophages promotes atherosclerosis by limiting translation control-dependent retardation of inflammation. Arterioscler Thromb Vasc Biol 34:533-42
Mazumder, Barsanjit; Poddar, Darshana; Basu, Abhijit et al. (2014) Extraribosomal l13a is a specific innate immune factor for antiviral defense. J Virol 88:9100-10
Das, Priyanka; Basu, Abhijit; Biswas, Aditi et al. (2013) Insights into the mechanism of ribosomal incorporation of mammalian L13a protein during ribosome biogenesis. Mol Cell Biol 33:2829-42
Poddar, Darshana; Basu, Abhijit; Baldwin 3rd, William M et al. (2013) An extraribosomal function of ribosomal protein L13a in macrophages resolves inflammation. J Immunol 190:3600-12
Basu, Abhijit; Das, Priyanka; Chaudhuri, Sujan et al. (2011) Requirement of rRNA methylation for 80S ribosome assembly on a cohort of cellular internal ribosome entry sites. Mol Cell Biol 31:4482-99
Mazumder, Barsanjit; Li, Xiaoxia; Barik, Sailen (2010) Translation control: a multifaceted regulator of inflammatory response. J Immunol 184:3311-9
Wan, Youzhong; Xiao, Hui; Affolter, Jeremy et al. (2009) Interleukin-1 receptor-associated kinase 2 is critical for lipopolysaccharide-mediated post-transcriptional control. J Biol Chem 284:10367-75
Vyas, Keyur; Chaudhuri, Sujan; Leaman, Douglas W et al. (2009) Genome-wide polysome profiling reveals an inflammation-responsive posttranscriptional operon in gamma interferon-activated monocytes. Mol Cell Biol 29:458-70
Galkin, Oleksandr; Bentley, Amber A; Gupta, Sujatha et al. (2007) Roles of the negatively charged N-terminal extension of Saccharomyces cerevisiae ribosomal protein S5 revealed by characterization of a yeast strain containing human ribosomal protein S5. RNA 13:2116-28
Chaudhuri, Sujan; Vyas, Keyur; Kapasi, Purvi et al. (2007) Human ribosomal protein L13a is dispensable for canonical ribosome function but indispensable for efficient rRNA methylation. RNA 13:2224-37

Showing the most recent 10 out of 13 publications