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Cited by 34RNA Research and SplicingGenetics, Aging, and Longevity in Model OrganismsNeuroscience and Neuropharmacology Research

SRSF11 Loss Leads to Aging-Associated Cognitive Decline by Modulating LRP8 and ApoE

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Raihan, Obayed, Brishti, Afrina, Li, Qin, Zhang, Qilun, Li, Dingfeng, Li, Xiaohui, Zhang, Qingyang, Xie, Zhongwen +3 more·2019·Cell Reports
DOI 10.1016/j.celrep.2019.06.002
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Abstract

RNA binding proteins, the key regulators in gene expression at the posttranscriptional level, remain largely uncharacterized with respect to aging and relevant cognitive deterioration. Here, we report that the levels of SFRS11 are substantially decreased in the prefrontal cortex (PFC) of aged brains. Notably, mice with SFRS11 deficiency in the PFC show impaired learning and memory. We demonstrate that SFRS11 directly binds to the 3' UTR of LRP8 mRNA, as well as to the third exon of apoE mRNA, resulting in stabilization of these mRNAs, eventually deactivating JNK signaling. Importantly, restoration of LRP8 and apoE reduces JNK signaling that is significantly enhanced in SFRS11-deficient cells. In addition, LRP8 and apoE rescue aging-like phenotypes induced by SFRS11 loss. Our findings demonstrate that age-dependent loss of SFRS11 in the PFC reduces levels of apoE and LRP8, leading to activation of the JNK pathway, ultimately influencing cognitive deficits.

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  1. [1]1. Amenta, F. ∙ Bronzetti, E. ∙ Sabbatini, M. ... Astrocyte changes in aging cerebral cortex and hippocampus: a quantitative immunohistochemical study Microsc. Res. Tech. 1998; 43:29-33 Crossref Scopus (92) PubMed Google Scholar
  2. [2]2. Basak, J.M. ∙ Verghese, P.B. ∙ Yoon, H. ... Low-density lipoprotein receptor represents an apolipoprotein E-independent pathway of Aβ uptake and degradation by astrocytes J. Biol. Chem. 2012; 287:13959-13971 Crossref Scopus (154) PubMed Google Scholar
  3. [3]3. Beffert, U. ∙ Nematollah Farsian, F. ∙ Masiulis, I. ... ApoE receptor 2 controls neuronal survival in the adult brain Curr. Biol. 2006; 16:2446-2452 Full Text Full Text (PDF) Scopus (73) PubMed Google Scholar
  4. [4]4. Blanco, F.J. ∙ Bernabéu, C. The splicing factor SRSF1 as a marker for endothelial senescence Front. Physiol. 2012; 3:54 Crossref Scopus (39) PubMed Google Scholar
  5. [5]5. Boisvert, M.M. ∙ Erikson, G.A. ∙ Shokhirev, M.N. ... The aging astrocyte transcriptome from multiple regions of the mouse brain Cell Rep. 2018; 22:269-285 Full Text Full Text (PDF) Scopus (438) PubMed Google Scholar
  6. [6]6. Chung, H.Y. ∙ Cesari, M. ∙ Anton, S. ... Molecular inflammation: underpinnings of aging and age-related diseases Ageing Res. Rev. 2009; 8:18-30 Crossref Scopus (953) PubMed Google Scholar
  7. [7]7. Cohen, R.M. ∙ Small, C. ∙ Lalonde, F. ... Effect of apolipoprotein E genotype on hippocampal volume loss in aging healthy women Neurology. 2001; 57:2223-2228 Crossref Scopus (151) PubMed Google Scholar
  8. [8]8. Colombo, E. ∙ Farina, C. Astrocytes: key regulators of neuroinflammation Trends Immunol. 2016; 37:608-620 Full Text Full Text (PDF) Scopus (620) PubMed Google Scholar
  9. [9]9. Cookson, M.R. RNA-binding proteins implicated in neurodegenerative diseases Wiley Interdiscip. Rev. RNA. 2017; 8:1 Crossref Scopus (41) Google Scholar
  10. [10]10. Edelsbrunner, M.E. ∙ Painsipp, E. ∙ Herzog, H. ... Evidence from knockout mice for distinct implications of neuropeptide-Y Y2 and Y4 receptors in the circadian control of locomotion, exploration, water and food intake Neuropeptides. 2009; 43:491-497 Crossref Scopus (44) PubMed Google Scholar
  11. [11]11. Espeseth, T. ∙ Westlye, L.T. ∙ Fjell, A.M. ... Accelerated age-related cortical thinning in healthy carriers of apolipoprotein E epsilon 4 Neurobiol. Aging. 2008; 29:329-340 Crossref Scopus (121) PubMed Google Scholar
  12. [13]13. Gordon, I. ∙ Grauer, E. ∙ Genis, I. ... Memory deficits and cholinergic impairments in apolipoprotein E-deficient mice Neurosci. Lett. 1995; 199:1-4 Crossref Scopus (191) PubMed Google Scholar
  13. [14]14. Gorospe, M. RNA-binding proteins: post-transcriptional control of aging traits: an introduction to a series of review articles Ageing Res. Rev. 2012; 11:421-422 Crossref Scopus (4) PubMed Google Scholar
  14. [15]15. Guo, P. ∙ El-Gohary, Y. ∙ Prasadan, K. ... Rapid and simplified purification of recombinant adeno-associated virus J. Virol. Methods. 2012; 183:139-146 Crossref Scopus (89) PubMed Google Scholar
  15. [16]16. Hayakawa, N. ∙ Kato, H. ∙ Araki, T. Age-related changes of astorocytes, oligodendrocytes and microglia in the mouse hippocampal CA1 sector Mech. Ageing Dev. 2007; 128:311-316 Crossref Scopus (89) PubMed Google Scholar
  16. [17]17. Huang, Y. ∙ Steitz, J.A. SRprises along a messenger’s journey Mol. Cell. 2005; 17:613-615 Full Text Full Text (PDF) Scopus (229) PubMed Google Scholar
  17. [18]18. Kawano, T. ∙ Fujita, M. ∙ Sakamoto, H. Unique and redundant functions of SR proteins, a conserved family of splicing factors, in Caenorhabditis elegans development Mech. Dev. 2000; 95:67-76 Crossref Scopus (30) PubMed Google Scholar
  18. [19]19. Le Pichon, C.E. ∙ Meilandt, W.J. ∙ Dominguez, S. ... Loss of dual leucine zipper kinase signaling is protective in animal models of neurodegenerative disease Sci. Transl. Med. 2017; 9:403 Crossref Scopus (94) Google Scholar
  19. [20]20. Lee, J.H. ∙ Jeong, S.A. ∙ Khadka, P. ... Involvement of SRSF11 in cell cycle-specific recruitment of telomerase to telomeres at nuclear speckles Nucleic Acids Res. 2015; 43:8435-8451 Crossref Scopus (16) PubMed Google Scholar
  20. [21]21. Leo, L.M. ∙ Pamplona, F.A. Elevated plus maze test to assess anxiety-like behavior in the mouse Bio Protoc. 2014; 4:e1211 Crossref Google Scholar
  21. [22]22. Liu, Q. ∙ Zhang, J. ∙ Zerbinatti, C. ... Lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis in the adult central nervous system PLoS Biol. 2011; 9:e1000575 Crossref Scopus (66) PubMed Google Scholar
  22. [23]23. Long, J.C. ∙ Caceres, J.F. The SR protein family of splicing factors: master regulators of gene expression Biochem. J. 2009; 417:15-27 Crossref Scopus (882) PubMed Google Scholar
  23. [24]24. Longman, D. ∙ McGarvey, T. ∙ McCracken, S. ... Multiple interactions between SRm160 and SR family proteins in enhancer-dependent splicing and development of C. elegans Curr. Biol. 2001; 11:1923-1933 Full Text Full Text (PDF) Scopus (37) PubMed Google Scholar
  24. [25]25. Lopez-Mejia, I.C. ∙ Vautrot, V. ∙ De Toledo, M. ... A conserved splicing mechanism of the LMNA gene controls premature aging Hum. Mol. Genet. 2011; 20:4540-4555 Crossref Scopus (63) PubMed Google Scholar
  25. [26]26. Love, S. ∙ Siew, L.K. ∙ Dawbarn, D. ... Premorbid effects of APOE on synaptic proteins in human temporal neocortex Neurobiol. Aging. 2006; 27:797-803 Crossref Scopus (83) PubMed Google Scholar
  26. [27]27. Maamar, H. ∙ Cabili, M.N. ∙ Rinn, J. ... linc-HOXA1 is a noncoding RNA that represses Hoxa1 transcription in cis Genes Dev. 2013; 27:1260-1271 Crossref Scopus (116) PubMed Google Scholar
  27. [28]28. Masliah, E. ∙ Mallory, M. ∙ Ge, N. ... Neurodegeneration in the central nervous system of apoE-deficient mice Exp. Neurol. 1995; 136:107-122 Crossref Scopus (364) PubMed Google Scholar
  28. [29]29. Masuda, K. ∙ Marasa, B. ∙ Martindale, J.L. ... Tissue- and age-dependent expression of RNA-binding proteins that influence mRNA turnover and translation Aging (Albany N.Y.). 2009; 1:681-698 Crossref Scopus (66) PubMed Google Scholar
  29. [30]30. McEwen, B.S. ∙ Morrison, J.H. The brain on stress: vulnerability and plasticity of the prefrontal cortex over the life course Neuron. 2013; 79:16-29 Full Text Full Text (PDF) Scopus (714) PubMed Google Scholar
  30. [31]31. Oh, S.W. ∙ Mukhopadhyay, A. ∙ Svrzikapa, N. ... JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16 Proc. Natl. Acad. Sci. USA. 2005; 102:4494-4499 Crossref Scopus (446) PubMed Google Scholar
  31. [32]32. Rawle, M.J. ∙ Davis, D. ∙ Bendayan, R. ... Apolipoprotein-E (Apoe) ε4 and cognitive decline over the adult life course Transl. Psychiatry. 2018; 8:18 Crossref Scopus (90) PubMed Google Scholar
  32. [33]33. Rodrigue, K.M. ∙ Raz, N. Shrinkage of the entorhinal cortex over five years predicts memory performance in healthy adults J. Neurosci. 2004; 24:956-963 Crossref Scopus (213) PubMed Google Scholar
  33. [36]36. Telese, F. ∙ Ma, Q. ∙ Perez, P.M. ... LRP8-reelin-regulated neuronal enhancer signature underlying learning and memory formation Neuron. 2015; 86:696-710 Full Text Full Text (PDF) Scopus (110) PubMed Google Scholar
  34. [37]37. Trommsdorff, M. ∙ Gotthardt, M. ∙ Hiesberger, T. ... Reeler/Disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2 Cell. 1999; 97:689-701 Full Text Full Text (PDF) Scopus (1118) PubMed Google Scholar
  35. [38]38. Tsuda, M.C. ∙ Ogawa, S. Long-lasting consequences of neonatal maternal separation on social behaviors in ovariectomized female mice PLoS ONE. 2012; 7:e33028 Crossref Scopus (64) PubMed Google Scholar
  36. [39]39. Vorhees, C.V. ∙ Williams, M.T. Morris water maze: procedures for assessing spatial and related forms of learning and memory Nat. Protoc. 2006; 1:848-858 Crossref Scopus (3373) PubMed Google Scholar
  37. [40]40. Wang, M.C. ∙ Bohmann, D. ∙ Jasper, H. JNK signaling confers tolerance to oxidative stress and extends lifespan in Drosophila Dev. Cell. 2003; 5:811-816 Full Text Full Text (PDF) Scopus (346) PubMed Google Scholar
  38. [41]41. Wee, C.D. ∙ Havens, M.A. ∙ Jodelka, F.M. ... Targeting SR proteins improves SMN expression in spinal muscular atrophy cells PLoS ONE. 2014; 9:e115205 Crossref Scopus (48) PubMed Google Scholar
  39. [42]42. Wu, J.Y. ∙ Maniatis, T. Specific interactions between proteins implicated in splice site selection and regulated alternative splicing Cell. 1993; 75:1061-1070

Authors
Raihan, O., Brishti, A., Li, Q., Zhang, Q., Li, D., Li, X., Zhang, Q., Xie, Z., Li, J., Zhang, J., & Liu, Q.
Affiliations
  • University of Science and Technology of China (CN)
  • Anhui Agricultural University (CN)
  • Kunming Institute of Zoology (CN)
Corresponding author
  • Zhang, Juan
  • Liu, Qiang
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2019-07
Volume
28
Issue
1
Pages
78-90.e6
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2019.06.002
OpenAlex
W2954984107
Cited by
34
References
46
Citations by year
2026: 1 · 2025: 11 · 2024: 5 · 2023: 2 · 2022: 8 · 2021: 3 · 2020: 4
FWCI
1.24
Type
journal article
Language
en
Update notices
erratum (2020-06-16)
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Chinese Academy of Sciences
  • Ministry of Science and Technology of the People's Republic of China
  • National Natural Science Foundation of China
  • Hefei Center for Physical Science and Technology
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
LRP8, apolipoprotein E, aging, cognitive decline, prefrontal cortex, RNA-binding proteins, post-transcriptional regulation, mRNA stabilization, 3' untranslated region, JNK signaling, learning and memory, age-related cognitive impairment
MeSH terms
Serine-Arginine Splicing Factors, Aging, Animals, Apolipoproteins E, Cell Line, Exons, Humans, Memory, Mice, Inbred C57BL, Neurons, Signal Transduction, Prefrontal Cortex, Mice, Knockout, Maze Learning, 3' Untranslated Regions, MAP Kinase Signaling System, LDL-Receptor Related Proteins, MAP Kinase Kinase 4, Mice, Gene Knockdown Techniques, Cognitive Dysfunction, Gene Ontology

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