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Intra- and inter-molecular regulation by intrinsically-disordered regions governs PUF protein RNA binding – Nature Communications

  • Xue, B., Dunker, A. K. & Uversky, V. N. Orderly order in protein intrinsic disorder distribution: disorder in 3500 proteomes from viruses and the three domains of life. J. Biomol. Struct. Dyn. 30, 137–149 (2012).

    Article  CAS  Google Scholar 

  • Wright, P. E. & Dyson, H. J. Intrinsically disordered proteins in cellular signalling and regulation. Nat. Rev. Mol. Cell Biol. 16, 18–29 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Babu, M. M. The contribution of intrinsically disordered regions to protein function, cellular complexity, and human disease. Biochem. Soc. Trans. 44, 1185–1200 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, C., Uversky, V. N. & Kurgan, L. Disordered nucleiome: abundance of intrinsic disorder in the DNA- and RNA-binding proteins in 1121 species from Eukaryota, Bacteria and Archaea. Proteomics 16, 1486–1498 (2016).

    Article  CAS  PubMed  Google Scholar 

  • Calabretta, S. & Richard, S. Emerging roles of disordered sequences in RNA-binding proteins. Trends Biochem. Sci. 40, 662–672 (2015).

    Article  CAS  PubMed  Google Scholar 

  • Jarvelin, A. I., Noerenberg, M., Davis, I. & Castello, A. The new (dis)order in RNA regulation. Cell Commun. Signal 14, 9 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  • Hentze, M. W., Castello, A., Schwarzl, T. & Preiss, T. A brave new world of RNA-binding proteins. Nat. Rev. Mol. Cell Biol. 19, 327–341 (2018).

    Article  CAS  Google Scholar 

  • Ottoz, D. S. M. & Berchowitz, L. E. The role of disorder in RNA binding affinity and specificity. Open Biol. 10, 200328 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zaharias, S. et al. Intrinsically disordered electronegative clusters improve stability and binding specificity of RNA-binding proteins. J. Biol. Chem. 297, 100945 (2021).

    Article  CAS  PubMed Central  Google Scholar 

  • Protter, D. S. W. et al. Intrinsically disordered regions can contribute promiscuous interactions to RNP granule assembly. Cell Rep. 22, 1401–1412 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lashkevich, K. A. & Dmitriev, S. E. mRNA targeting, transport and local translation in eukaryotic cells: from the classical view to a diversity of new concepts. Mol. Biol. 55, 507–537 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roy, B. & Jacobson, A. The intimate relationships of mRNA decay and translation. Trends Genet. 29, 691–699 (2013).

    Article  CAS  PubMed  Google Scholar 

  • Li, W., Deng, X. & Chen, J. RNA-binding proteins in regulating mRNA stability and translation: roles and mechanisms in cancer. Semin. Cancer Biol. 86, 664–677 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Campbell, Z. T. et al. Cooperativity in RNA-protein interactions: global analysis of RNA binding specificity. Cell Rep. 1, 570–581 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weidmann, C. A. et al. Drosophila Nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of Pumilio. eLife 5, e17096 (2016).

    Article  PubMed Central  Google Scholar 

  • Hennig, J. et al. Structural basis for the assembly of the Sxl-Unr translation regulatory complex. Nature 515, 287–290 (2014).

    Article  ADS  CAS  PubMed  Google Scholar 

  • Qiu, C. et al. A crystal structure of a collaborative RNA regulatory complex reveals mechanisms to refine target specificity. eLife 8, e48968 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qiu, C., Wine, R. N., Campbell, Z. T. & Hall, T. M. T. Bipartite interaction sites differentially modulate RNA-binding affinity of a protein complex essential for germline stem cell self-renewal. Nucleic Acids Res. 50, 536–548 (2022).

    Article  CAS  PubMed  Google Scholar 

  • Crittenden, S. L. et al. A conserved RNA-binding protein controls germline stem cells in Caenorhabditis elegans. Nature 417, 660–663 (2002).

    Article  ADS  CAS  PubMed  Google Scholar 

  • Kershner, A. M., Shin, H., Hansen, T. J. & Kimble, J. Discovery of two GLP-1/Notch target genes that account for the role of GLP-1/Notch signaling in stem cell maintenance. Proc. Natl Acad. Sci. USA 111, 3739–3744 (2014).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Shin, H. et al. SYGL-1 and LST-1 link niche signaling to PUF RNA repression for stem cell maintenance in Caenorhabditis elegans. PLoS Genet. 13, e1007121 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  • Haupt, K. A. et al. The molecular basis of LST-1 self-renewal activity and its control of stem cell pool size. Development 146, dev181644 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferdous A. S. et al. The in vivo functional significance of PUF hub partnerships in C. elegans germline stem cells. Development 150, dev201705 (2023).

  • Albarqi, M. M. Y. & Ryder, S. P. The role of RNA-binding proteins in orchestrating germline development in Caenorhabditis elegans. Front Cell Dev. Biol. 10, 1094295 (2022).

    Article  PubMed  Google Scholar 

  • Barker, D. D., Wang, C., Moore, J., Dickinson, L. K. & Lehmann, R. Pumilio is essential for function but not for distribution of the Drosophila abdominal determinant Nanos. Genes Dev. 6, 2312–2326 (1992).

    Article  CAS  PubMed  Google Scholar 

  • Goldstrohm, A. C., Hall, T. M. T. & McKenney, K. M. Post-transcriptional regulatory functions of mammalian pumilio proteins. Trends Genet. 34, 972–990 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Macdonald, P. M. The Drosophila pumilio gene: an unusually long transcription unit and an unusual protein. Development 114, 221–232 (1992).

    Article  CAS  PubMed  Google Scholar 

  • Zamore, P. D., Williamson, J. R. & Lehmann, R. The Pumilio protein binds RNA through a conserved domain that defines a new class of RNA-binding proteins. RNA 3, 1421–1433 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, B. et al. A conserved RNA-binding protein that regulates sexual fates in the C. elegans hermaphrodite germ line. Nature 390, 477–484 (1997).

    Article  ADS  CAS  PubMed  Google Scholar 

  • Wickens, M., Bernstein, D. S., Kimble, J. & Parker, R. A. PUF family portrait: 3’UTR regulation as a way of life. Trends Genet. 18, 150–157 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Wang, M., Oge, L., Perez-Garcia, M. D., Hamama, L. & Sakr, S. The PUF protein family: overview on PUF RNA targets, biological functions, and post transcriptional regulation. Int. J. Mol. Sci. 19, 410 (2018).

    Article  PubMed Central  Google Scholar 

  • Edwards, T. A., Pyle, S. E., Wharton, R. P. & Aggarwal, A. K. Structure of Pumilio reveals similarity between RNA and peptide binding motifs. Cell 105, 281–289 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Wang, X., McLachlan, J., Zamore, P. D. & Hall, T. M. Modular recognition of RNA by a human Pumilio-homology domain. Cell 110, 501–512 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Wang, X., Zamore, P. D. & Hall, T. M. Crystal structure of a Pumilio homology domain. Mol. Cell 7, 855–865 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Bernstein, D., Hook, B., Hajarnavis, A., Opperman, L. & Wickens, M. Binding specificity and mRNA targets of a C. elegans PUF protein, FBF-1. RNA 11, 447–458 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prasad, A. et al. The PUF binding landscape in metazoan germ cells. RNA 22, 1026–1043 (2016).

    Article  CAS  PubMed Central  Google Scholar 

  • Opperman, L., Hook, B., DeFino, M., Bernstein, D. S. & Wickens, M. A single spacer nucleotide determines the specificities of two mRNA regulatory proteins. Nat. Struct. Mol. Biol. 12, 945–951 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Suh, N. et al. FBF and its dual control of gld-1 expression in the Caenorhabditis elegans germline. Genetics 181, 1249–1260 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, Y., Opperman, L., Wickens, M. & Hall, T. M. Structural basis for specific recognition of multiple mRNA targets by a PUF regulatory protein. Proc. Natl Acad. Sci. USA 106, 20186–20191 (2009).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Qiu, C. et al. Divergence of Pumilio/fem-3 mRNA binding factor (PUF) protein specificity through variations in an RNA-binding pocket. J. Biol. Chem. 287, 6949–6957 (2012).

    Article  CAS  PubMed  Google Scholar 

  • Wang, X. et al. Dynein light chain DLC-1 promotes localization and function of the PUF protein FBF-2 in germline progenitor cells. Development 143, 4643–4653 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Varadi, M. et al. AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models. Nucleic Acids Res. 50, D439–D444 (2022).

    Article  CAS  PubMed  Google Scholar 

  • Ramos, A., Hollingworth, D. & Pastore, A. G-quartet-dependent recognition between the FMRP RGG box and RNA. RNA 9, 1198–1207 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shen, H., Kan, J. L. & Green, M. R. Arginine-serine-rich domains bound at splicing enhancers contact the branchpoint to promote prespliceosome assembly. Mol. Cell 13, 367–376 (2004).

    Article  CAS  Google Scholar 

  • Zhang, J. et al. Molecular mechanisms for the regulation of histone mRNA stem-loop-binding protein by phosphorylation. Proc. Natl Acad. Sci. USA 111, E2937–E2946 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stowell, J. A. W. et al. A low-complexity region in the YTH domain protein Mmi1 enhances RNA binding. J. Biol. Chem. 293, 9210–9222 (2018).

    Article  CAS  PubMed Central  Google Scholar 

  • Santiago-Frangos, A., Jeliazkov, J. R., Gray, J. J. & Woodson, S. A. Acidic C-terminal domains autoregulate the RNA chaperone Hfq. eLife 6, e27049 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang, J., Gonzalez, L. E. & Hall, T. M. T. Structural analysis reveals the flexible C-terminus of Nop15 undergoes rearrangement to recognize a pre-ribosomal RNA folding intermediate. Nucleic Acids Res. 45, 2829–2837 (2017).

    CAS  PubMed  Google Scholar 

  • Luitjens, C., Gallegos, M., Kraemer, B., Kimble, J. & Wickens, M. CPEB proteins control two key steps in spermatogenesis in C. elegans. Genes Dev. 14, 2596–2609 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eckmann, C. R., Crittenden, S. L., Suh, N. & Kimble, J. GLD-3 and control of the mitosis/meiosis decision in the germline of Caenorhabditis elegans. Genetics 168, 147–160 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Campbell, Z. T. et al. Identification of a conserved interface between PUF and CPEB proteins. J. Biol. Chem. 287, 18854–18862 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Menichelli, E., Wu, J., Campbell, Z. T., Wickens, M. & Williamson, J. R. Biochemical characterization of the Caenorhabditis elegans FBF.CPB-1 translational regulation complex identifies conserved protein interaction hotspots. J. Mol. Biol. 425, 725–737 (2013).

    Article  CAS  PubMed  Google Scholar 

  • Wu, J., Campbell, Z. T., Menichelli, E., Wickens, M. & Williamson, J. R. A protein.protein interaction platform involved in recruitment of GLD-3 to the FBF.fem-3 mRNA complex. J. Mol. Biol. 425, 738–754 (2013).

    Article  CAS  Google Scholar 

  • Haupt, K. A. et al. A PUF hub drives self-renewal in Caenorhabditis elegans germline stem cells. Genetics 214, 147–161 (2020).

    Article  CAS  Google Scholar 

  • Voronina, E., Paix, A. & Seydoux, G. The P granule component PGL-1 promotes the localization and silencing activity of the PUF protein FBF-2 in germline stem cells. Development 139, 3732–3740 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, X. et al. Antagonistic control of Caenorhabditis elegans germline stem cell proliferation and differentiation by PUF proteins FBF-1 and FBF-2. eLife 9, e52788 (2020).

    Article  CAS  PubMed Central  Google Scholar 

  • Blom, N., Gammeltoft, S. & Brunak, S. Sequence and structure-based prediction of eukaryotic protein phosphorylation sites. J. Mol. Biol. 294, 1351–1362 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Blom, N., Sicheritz-Ponten, T., Gupta, R., Gammeltoft, S. & Brunak, S. Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence. Proteomics 4, 1633–1649 (2004).

    Article  CAS  Google Scholar 

  • Koh, Y. Y. et al. A single C. elegans PUF protein binds RNA in multiple modes. RNA 15, 1090–1099 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bhat, V. D. et al. Engineering a conserved RNA regulatory protein repurposes its biological function in vivo. eLife 8, e43788 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  • Stumpf, C. R., Kimble, J. & Wickens, M. A. Caenorhabditis elegans PUF protein family with distinct RNA binding specificity. RNA 14, 1550–1557 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mossessova, E. & Lima, C. D. Ulp1-SUMO crystal structure and genetic analysis reveal conserved interactions and a regulatory element essential for cell growth in yeast. Mol. Cell 5, 865–876 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307–326 (1997).

    Article  CAS  PubMed  Google Scholar 

  • McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658–674 (2007).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213–221 (2010).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126–2132 (2004).

    Article  ADS  PubMed  Google Scholar 

  • Case, D. A. et al. AMBER 2020. (eds) (2020).

  • Yang, H. & Song, Y. Structural insight for roles of DR5 death domain mutations on oligomerization of DR5 death domain-FADD complex in the death-inducing signaling complex formation: a computational study. J. Mol. Model 22, 89 (2016).

    Article  PubMed  Google Scholar 

  • Erdos, G. & Dosztanyi, Z. Analyzing protein disorder with IUPred2A. Curr. Protoc. Bioinf. 70, e99 (2020).

    Article  CAS  Google Scholar 

  • Meszaros, B., Erdos, G. & Dosztanyi, Z. IUPred2A: context-dependent prediction of protein disorder as a function of redox state and protein binding. Nucleic Acids Res. 46, W329–W337 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferdous, A. S. et al. LST-1 is a bifunctional regulator that feeds back on Notch-dependent transcription to regulate C. elegans germline stem cells. Proc. Natl Acad. Sci. USA 120, e2309964120 (2023).

    Article  CAS  PubMed Central  Google Scholar