Functions, mechanisms and regulation of Pumilio/Puf family RNA binding proteins: a comprehensive review

Nishanth, M. J.; Simon, Bindu

doi:10.1007/s11033-019-05142-6

Cited by 35 publications

(21 citation statements)

References 127 publications

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“…Catalase-rel domains are predicted to catalyze the degradation of reactive oxygen species (ROS) [ 29 , 30 ]. DUF has a distant homology to globin-like domains and Puf-family RNA-binding domains, which influence the stability of eukaryotic RNAs [ 31 , 32 ]. Finally, STE domains mediate transcriptional induction in yeast [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

Evolution-guided mutagenesis of the cytoplasmic incompatibility proteins: Identifying CifA’s complex functional repertoire and new essential regions in CifB

2020

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Wolbachia are the world's most common, maternally-inherited, arthropod endosymbionts. Their worldwide distribution is due, in part, to a selfish drive system termed cytoplasmic incompatibility (CI) that confers a relative fitness advantage to females that transmit Wolbachia to their offspring. CI results in embryonic death when infected males mate with uninfected females but not infected females. Under the Two-by-One genetic model of CI, males expressing the two phage WO proteins CifA and CifB cause CI, and females expressing CifA rescue CI. While each protein is predicted to harbor three functional domains, there is no knowledge on how sites across these Cif domains, rather than in any one particular domain, contribute to CI and rescue. Here, we use evolution-guided, substitution mutagenesis of conserved amino acids across the Cif proteins, coupled with transgenic expression in uninfected Drosophila melanogaster, to determine the functional impacts of conserved residues evolving mostly under purifying selection. We report that amino acids in CifA's N-terminal unannotated region and annotated catalase-related domain are important for both complete CI and rescue, whereas C-terminal residues in CifA's putative domain of unknown function are solely important for CI. Moreover, conserved CifB amino acids in the predicted nucleases, peptidase, and unannotated regions are essential for CI. Taken together, these findings indicate that (i) all CifA amino acids determined to be crucial in rescue are correspondingly crucial in CI, (ii) an additional set of CifA amino acids are uniquely important in CI, and (iii) CifB amino acids across the protein, rather than in one particular domain, are all crucial for CI. We discuss how these findings advance an expanded view of Cif protein evolution and function, inform the mechanistic and biochemical bases of Cif-induced CI/rescue, and continue to substantiate the Two-by-One genetic model of CI.

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Section: Introductionmentioning

confidence: 99%

Evolution-guided mutagenesis of the cytoplasmic incompatibility proteins: Identifying CifA’s complex functional repertoire and new essential regions in CifB

2020

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Section: Discussionmentioning

confidence: 99%

“…These RBPs facilitate the translational repression, deadenylation, and subsequent decay of target transcripts through recruitment of the CCR4-NOT complex. 23 , 24 A yeast Pumilio orthologue has previously been described as mediating the translational repression of genes linked to oxidative stress. 25 Furthermore, it is known that upon oxidative stress, mammalian Pumilio proteins, which are structurally conserved but functionally divergent with their yeast orthologues, localize to SGs.…”

Section: Discussionmentioning

confidence: 99%

RNA Binding Proteins As Regulators of Oxidative Stress Identified by a Targeted CRISPR-Cas9 Single Guide RNA Library

Turner

2021

The CRISPR Journal

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The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 genome editing system has been broadly adopted for high-throughput genetic screens. However, the application of genome-wide single guide RNA (sgRNA) libraries can be challenging. We generated a custom sgRNA library, an order of magnitude smaller than genome-wide alternatives, to facilitate the genetic screening of RNA binding proteins (RBPs). We demonstrated the utility of our reagent in a genetic screen for RBPs that conveyed cellular resistance or sensitivity to oxidative stress induced by paraquat. This identified that CSDE1 and STRAP, proteins that interact with each other, convey sensitivity to oxidative stress and that Pumilio homologues (PUM1 and PUM2) convey resistance. Targeting eIF4-E1 and -A1 protected cells from high-dose paraquat, whereas eIF4E2 targeted cells did less well. We also found that G3BP1 promoted sensitivity to a low dose of paraquat but protected cells at a higher dose. Our study highlights the use of genetic screens to identify roles of RBPs and identifies novel genes regulating sensitivity to oxidative stress.

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“…The Pumilio proteins repress target mRNAs by antagonizing the translation and promoting RNA degradation. 46,47 The Pumilio family RNA-binding protein PUF3 can select the appropriate mRNAs from the many. The results of the binding kinetics analysis reveal that this is primarily due to differences in dissociation rate constants.…”

Section: Mrna Deadenylationmentioning

confidence: 99%

mRNPs: Structure and role in development

Voronina

Pshennikova

2021

Cell Biochemistry & Function

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In eukaryotic cells, mRNA molecules are coated with numerous RNA‐binding proteins and so exist in ribonucleoproteins (mRNPs). The proteins associated with the mRNA regulate the fate of mRNA, including its localization, translation and decay. Before activation of translation, the mRNA does not display any template functions—it is masked. The coordinated activity of certain RNA‐binding proteins determines the future fate of each mRNA individually. In embryo development, the temporal and spatial regulation of translation can cause a situation when the mRNA and the encoded protein are localized in different compartments and so the differentiation of the cells can be determined. The fundamentals of regulation of the mRNAs fate and functioning in nerves are similar to those already described for oo‐ and embryogenesis. Disorders in the mRNA masking and demasking result in the emergence of various diseases, in particular cancers and neuro‐degenerative diseases.

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Functions, mechanisms and regulation of Pumilio/Puf family RNA binding proteins: a comprehensive review

Cited by 35 publications

References 127 publications

Evolution-guided mutagenesis of the cytoplasmic incompatibility proteins: Identifying CifA’s complex functional repertoire and new essential regions in CifB

Evolution-guided mutagenesis of the cytoplasmic incompatibility proteins: Identifying CifA’s complex functional repertoire and new essential regions in CifB

RNA Binding Proteins As Regulators of Oxidative Stress Identified by a Targeted CRISPR-Cas9 Single Guide RNA Library

mRNPs: Structure and role in development

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