Neurodegenerative Diseases: Quantitative Predictions of Protein-RNA Interactions

Overview

Journal RNA

Specialty Molecular Biology

Date 2012 Dec 25

PMID 23264567

Citations 43

Authors

Davide Cirillo

Federico Agostini

Petr Klus

Domenica Marchese

Silvia Rodriguez

Benedetta Bolognesi

Gian Gaetano Tartaglia

Affiliations

Soon will be listed here.

Abstract

Increasing evidence indicates that RNA plays an active role in a number of neurodegenerative diseases. We recently introduced a theoretical framework, catRAPID, to predict the binding ability of protein and RNA molecules. Here, we use catRAPID to investigate ribonucleoprotein interactions linked to inherited intellectual disability, amyotrophic lateral sclerosis, Creutzfeuld-Jakob, Alzheimer's, and Parkinson's diseases. We specifically focus on (1) RNA interactions with fragile X mental retardation protein FMRP; (2) protein sequestration caused by CGG repeats; (3) noncoding transcripts regulated by TAR DNA-binding protein 43 TDP-43; (4) autogenous regulation of TDP-43 and FMRP; (5) iron-mediated expression of amyloid precursor protein APP and α-synuclein; (6) interactions between prions and RNA aptamers. Our results are in striking agreement with experimental evidence and provide new insights in processes associated with neuronal function and misfunction.

Citing Articles

Synchronized motion of interface residues for evaluating protein-RNA complex binding affinity: Application to aptamer-mediated inhibition of TDP-43 aggregates.

Panei F, Di Rienzo L, Zacco E, Armaos A, Tartaglia G, Ruocco G Protein Sci. 2024; 33(12):e5201.

PMID: 39548508 PMC: 11567837. DOI: 10.1002/pro.5201.

Predicting nuclear G-quadruplex RNA-binding proteins with roles in transcription and phase separation.

Luige J, Armaos A, Tartaglia G, Vang Orom U Nat Commun. 2024; 15(1):2585.

PMID: 38519458 PMC: 10959947. DOI: 10.1038/s41467-024-46731-9.

Prediction of protein-RNA interactions from single-cell transcriptomic data.

Fiorentino J, Armaos A, Colantoni A, Tartaglia G Nucleic Acids Res. 2024; 52(6):e31.

PMID: 38364867 PMC: 11014251. DOI: 10.1093/nar/gkae076.

HIF1α-AS1 is a DNA:DNA:RNA triplex-forming lncRNA interacting with the HUSH complex.

Leisegang M, Bains J, Seredinski S, Oo J, Krause N, Kuo C Nat Commun. 2022; 13(1):6563.

PMID: 36323673 PMC: 9630315. DOI: 10.1038/s41467-022-34252-2.

Could Amyloid-β 1-42 or α-Synuclein Interact Directly with Mitochondrial DNA? A Hypothesis.

Gezen-Ak D, Yurttas Z, Camolu T, Dursun E ACS Chem Neurosci. 2022; 13(19):2803-2812.

PMID: 36125124 PMC: 9542719. DOI: 10.1021/acschemneuro.2c00512.

References

Kim H, Kim T, Joo Y, Shin H, Kim S, Jang C . RpS3 translation is repressed by interaction with its own mRNA. J Cell Biochem. 2010; 110(2):294-303. DOI: 10.1002/jcb.22537. View

Rogers J, Randall J, Cahill C, Eder P, Huang X, Gunshin H . An iron-responsive element type II in the 5'-untranslated region of the Alzheimer's amyloid precursor protein transcript. J Biol Chem. 2002; 277(47):45518-28. DOI: 10.1074/jbc.M207435200. View

Oostra B, Willemsen R . FMR1: a gene with three faces. Biochim Biophys Acta. 2009; 1790(6):467-77. PMC: 2692361. DOI: 10.1016/j.bbagen.2009.02.007. View

Strong M, Volkening K, Hammond R, Yang W, Strong W, Leystra-Lantz C . TDP43 is a human low molecular weight neurofilament (hNFL) mRNA-binding protein. Mol Cell Neurosci. 2007; 35(2):320-7. DOI: 10.1016/j.mcn.2007.03.007. View

Fiesel F, Kahle P . TDP-43 and FUS/TLS: cellular functions and implications for neurodegeneration. FEBS J. 2011; 278(19):3550-68. DOI: 10.1111/j.1742-4658.2011.08258.x. View

Tassone F, Hagerman R, Loesch D, Lachiewicz A, Taylor A, Hagerman P . Fragile X males with unmethylated, full mutation trinucleotide repeat expansions have elevated levels of FMR1 messenger RNA. Am J Med Genet. 2000; 94(3):232-6. DOI: 10.1002/1096-8628(20000918)94:3<232::aid-ajmg9>3.0.co;2-h. View

Ayala Y, De Conti L, Avendano-Vazquez S, Dhir A, Romano M, DAmbrogio A . TDP-43 regulates its mRNA levels through a negative feedback loop. EMBO J. 2010; 30(2):277-88. PMC: 3025456. DOI: 10.1038/emboj.2010.310. View

Buttarelli F, Circella A, Pellicano C, Pontieri F . Dopamine transporter immunoreactivity in peripheral blood mononuclear cells in amyotrophic lateral sclerosis. Eur J Neurol. 2006; 13(4):416-8. DOI: 10.1111/j.1468-1331.2006.01235.x. View

Lee E, Lee V, Trojanowski J . Gains or losses: molecular mechanisms of TDP43-mediated neurodegeneration. Nat Rev Neurosci. 2011; 13(1):38-50. PMC: 3285250. DOI: 10.1038/nrn3121. View

10.

Primerano B, Tassone F, Hagerman R, Hagerman P, Amaldi F, Bagni C . Reduced FMR1 mRNA translation efficiency in fragile X patients with premutations. RNA. 2003; 8(12):1482-8. PMC: 1370354. View

11.

Kryshtafovych A, Venclovas C, Fidelis K, Moult J . Progress over the first decade of CASP experiments. Proteins. 2005; 61 Suppl 7:225-236. DOI: 10.1002/prot.20740. View

12.

Philpott C, Klausner R, Rouault T . The bifunctional iron-responsive element binding protein/cytosolic aconitase: the role of active-site residues in ligand binding and regulation. Proc Natl Acad Sci U S A. 1994; 91(15):7321-5. PMC: 44391. DOI: 10.1073/pnas.91.15.7321. View

13.

Deleault N, Lucassen R, Supattapone S . RNA molecules stimulate prion protein conversion. Nature. 2003; 425(6959):717-20. DOI: 10.1038/nature01979. View

14.

Schaeffer C, Bardoni B, Mandel J, Ehresmann B, Ehresmann C, Moine H . The fragile X mental retardation protein binds specifically to its mRNA via a purine quartet motif. EMBO J. 2001; 20(17):4803-13. PMC: 125594. DOI: 10.1093/emboj/20.17.4803. View

15.

Tartaglia G, Pawar A, Campioni S, Dobson C, Chiti F, Vendruscolo M . Prediction of aggregation-prone regions in structured proteins. J Mol Biol. 2008; 380(2):425-36. DOI: 10.1016/j.jmb.2008.05.013. View

16.

Hagerman P, Hagerman R . The fragile-X premutation: a maturing perspective. Am J Hum Genet. 2004; 74(5):805-16. PMC: 1181976. DOI: 10.1086/386296. View

17.

Darnell J, Jensen K, Jin P, Brown V, Warren S, Darnell R . Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function. Cell. 2001; 107(4):489-99. DOI: 10.1016/s0092-8674(01)00566-9. View

18.

Sellier C, Rau F, Liu Y, Tassone F, Hukema R, Gattoni R . Sam68 sequestration and partial loss of function are associated with splicing alterations in FXTAS patients. EMBO J. 2010; 29(7):1248-61. PMC: 2857464. DOI: 10.1038/emboj.2010.21. View

19.

Mercey R, Lantier I, Maurel M, Grosclaude J, Lantier F, Marc D . Fast, reversible interaction of prion protein with RNA aptamers containing specific sequence patterns. Arch Virol. 2006; 151(11):2197-214. DOI: 10.1007/s00705-006-0790-3. View

20.

Jin P, Duan R, Qurashi A, Qin Y, Tian D, Rosser T . Pur alpha binds to rCGG repeats and modulates repeat-mediated neurodegeneration in a Drosophila model of fragile X tremor/ataxia syndrome. Neuron. 2007; 55(4):556-64. PMC: 1994817. DOI: 10.1016/j.neuron.2007.07.020. View