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Published on: January 19, 2015
Post-transcriptional Regulatory Functions of Mammalian Pumilio Proteins
Aaron C Goldstrohm1, Traci M Tanaka Hall2, Katherine M McKenney1
1Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
Abstract:
Mammalian Pumilio proteins, PUM1 and PUM2, are members of the PUF family of sequence-specific RNA-binding proteins. In this review, we explore their mechanisms, regulatory networks, biological functions, and relevance to diseases. Pumilio proteins bind an extensive network of mRNAs and repress protein expression by inhibiting translation and promoting mRNA decay. Opposingly, in certain contexts, they can activate protein expression. Pumilio proteins also regulate noncoding (nc)RNAs. The ncRNA, ncRNA activated by DNA damage (NORAD), can in turn modulate Pumilio activity. Genetic analysis provides new insights into Pumilio protein function. They are essential for growth and development. They control diverse processes, including stem cell fate, and neurological functions, such as behavior and memory formation. Novel findings show that their dysfunction contributes to neurodegeneration, epilepsy, movement disorders, intellectual disability, infertility, and cancer.
Insights
Mammalian Pumilio proteins (PUM1 and PUM2) are crucial RNA-binding proteins regulating gene expression. Their dysfunction is linked to various diseases, including neurodegeneration and cancer.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Pumilio proteins (PUM1, PUM2) are sequence-specific RNA-binding proteins belonging to the PUF family.
- These proteins play critical roles in post-transcriptional gene regulation by binding to messenger RNAs (mRNAs).
Purpose of the Study:
- To review the mechanisms, regulatory networks, biological functions, and disease relevance of mammalian Pumilio proteins.
- To highlight novel findings regarding Pumilio protein involvement in diverse physiological and pathological processes.
Main Methods:
- Literature review of existing research on Pumilio proteins.
- Analysis of genetic studies and their implications for Pumilio protein function.
- Exploration of regulatory interactions involving Pumilio proteins and noncoding RNAs (ncRNAs).
Main Results:
- Pumilio proteins primarily repress protein expression by inhibiting translation and promoting mRNA decay, but can activate expression in specific contexts.
- They regulate a vast network of mRNAs and also interact with ncRNAs, such as ncRNA activated by DNA damage (NORAD).
- Genetic analysis confirms Pumilio proteins are essential for growth, development, stem cell fate, and neurological functions like memory.
Conclusions:
- Pumilio proteins are vital regulators of gene expression with broad biological functions.
- Dysfunction of Pumilio proteins is implicated in a spectrum of diseases, including neurodegenerative disorders, epilepsy, intellectual disability, infertility, and cancer.
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