TY - JOUR
T1 - Slowly produced MicroRNAs control protein levels
AU - Whichard, Zakary L.
AU - Motter, Adilson E.
AU - Stein, Peter J.
AU - Corey, Seth J.
PY - 2011/2/11
Y1 - 2011/2/11
N2 - Proteins are the primary agents of function in biological systems, and their levels are critical control elements, reflecting the interplay between transcription, translation, and protein degradation. Here, we consider the role of microRNAs (miRNAs) in the post-transcriptional regulation of protein synthesis. To determine their impact on protein concentration, we constructed a mechanistic model consisting of four state variables and nine kinetic parameters that account for transcript sequestration and degradation via miRNA-mRNA complex formation. Our dynamical model predicts that, even when present in low copy number, miRNAs can exert potent effects on protein concentration. Sensitivity analysis of the steady-state solution indicates that miRNA synthesis commonly acts to fine-tune protein concentrations. However, the same analysis shows that for a small subset of miRNA-mRNA pairs characterized by slowly produced miRNAs, the miRNA synthesis rate is the dominant control element. Our model equations provide a tool to evaluate the importance of particular miRNAs on their target proteins and promote the development of miRNAbased therapies that target proteins associated with cancer, inflammation, and metabolic disorders.
AB - Proteins are the primary agents of function in biological systems, and their levels are critical control elements, reflecting the interplay between transcription, translation, and protein degradation. Here, we consider the role of microRNAs (miRNAs) in the post-transcriptional regulation of protein synthesis. To determine their impact on protein concentration, we constructed a mechanistic model consisting of four state variables and nine kinetic parameters that account for transcript sequestration and degradation via miRNA-mRNA complex formation. Our dynamical model predicts that, even when present in low copy number, miRNAs can exert potent effects on protein concentration. Sensitivity analysis of the steady-state solution indicates that miRNA synthesis commonly acts to fine-tune protein concentrations. However, the same analysis shows that for a small subset of miRNA-mRNA pairs characterized by slowly produced miRNAs, the miRNA synthesis rate is the dominant control element. Our model equations provide a tool to evaluate the importance of particular miRNAs on their target proteins and promote the development of miRNAbased therapies that target proteins associated with cancer, inflammation, and metabolic disorders.
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U2 - 10.1074/jbc.M110.166348
DO - 10.1074/jbc.M110.166348
M3 - Article
C2 - 21051536
AN - SCOPUS:79952999220
SN - 0021-9258
VL - 286
SP - 4742
EP - 4748
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 6
ER -