Combinatorial control of messenger RNAs by Pumilio, Nanos and Brain Tumor Proteins.
Eukaryotes possess a vast array of RNA-binding proteins (RBPs) that affect mRNAs in diverse ways to control protein expression. Combinatorial regulation of mRNAs by RBPs is emerging as the rule. No example illustrates this as vividly as the partnership of 3 Drosophila RBPs, Pumilio, Nanos and Brain Tumor, which have overlapping functions in development, stem cell maintenance and differentiation, fertility and neurologic processes. Here we synthesize 30 y of research with new insights into their molecular functions and mechanisms of action. First, we provide an overview of the key properties of each RBP. Next, we present a detailed analysis of their collaborative regulatory mechanism using a classic example of the developmental morphogen, hunchback, which is spatially and temporally regulated by the trio during embryogenesis. New biochemical, structural and functional analyses provide insights into RNA recognition, cooperativity, and regulatory mechanisms. We integrate these data into a model of combinatorial RNA binding and regulation of translation and mRNA decay. We then use this information, transcriptome wide analyses and bioinformatics predictions to assess the global impact of Pumilio, Nanos and Brain Tumor on gene regulation. Together, the results support pervasive, dynamic post-transcriptional control.
a Department of Biological Chemistry , University of Michigan , Ann Arbor , Michigan , USA.|d Department of Biochemistry, Molecular Biology and Biophysics , University of Minnesota , Minneapolis , Minnesota , USA.
René M
RM
Arvola
b Department of Chemistry , University of North Carolina , Chapel Hill , USA.
Chase A
0000-0002-2941-0500
CA
Weidmann
c Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences , National Institutes of Health , Research Triangle Park, North Carolina , USA.
Traci M
0000-0001-6166-3009
TM
Tanaka Hall
d Department of Biochemistry, Molecular Biology and Biophysics , University of Minnesota , Minneapolis , Minnesota , USA.
Aaron C
0000-0002-1867-8763
AC
Goldstrohm
D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D004625:Embryo, Nonmammalian; D047108:Embryonic Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D008958:Models, Molecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C412783:brat protein, Drosophila; C061245:hb protein, Drosophila; C074333:pum protein, Drosophila; C070574:nos protein, Drosophila
Brain Tumor (or Brat); Nanos; Pumilio; combinatorial mRNA regulation; cooperative RNA binding