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.
Bibliographical noteFunding Information:
We thank Peter Freddolino for discussions and input on this work. This work was supported by grant R01GM105707 from the National Institute of General Medical Sciences , National Institutes of Health (A.C.G.) and the Intramural Research Program of the National Institutes of Health , National Institute of Environmental Health Sciences (T.M.T.H.). We sincerely apologize to colleagues whose work we were unable to include due to space limitations.
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