• ISSN 1674-8301
  • CN 32-1810/R
Volume 36 Issue 4
Jul.  2022
Turn off MathJax
Article Contents
Yujuan Su, Xinghui Guo, Min Zang, Zhengyao Xie, Tingting Zhao, Eugene Yujun Xu. RNA binding protein BOULE forms aggregates in mammalian testis[J]. The Journal of Biomedical Research, 2022, 36(4): 255-268. doi: 10.7555/JBR.36.20220072
Citation: Yujuan Su, Xinghui Guo, Min Zang, Zhengyao Xie, Tingting Zhao, Eugene Yujun Xu. RNA binding protein BOULE forms aggregates in mammalian testis[J]. The Journal of Biomedical Research, 2022, 36(4): 255-268. doi: 10.7555/JBR.36.20220072

RNA binding protein BOULE forms aggregates in mammalian testis

doi: 10.7555/JBR.36.20220072
More Information
  • Corresponding author: Eugene Yujun Xu, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu 211166, China. Tel: +86-25-86869505, E-mail: e-xu@northwestern.edu
  • Received: 2022-04-05
  • Revised: 2022-05-25
  • Accepted: 2022-05-27
  • Published: 2022-06-28
  • Issue Date: 2022-07-28
  • Amyloids have traditionally been considered pathologic protein aggregates which contribute to neurodegeneration. New evidence however increasingly suggests that non-pathological amyloids are formed in animals during normal development. Amyloid-like aggregate formation was originally thought to be a conserved feature of animal gametogenesis. This hypothesis was based on findings which suggest that regulated amyloid formations govern yeast meiosis by way of meiosis-specific RNA binding proteins. Additional support came from studies which demonstrate that DAZL, a mammalian gametogenesis-specific RNA binding protein, also forms SDS-resistant aggregates in vivo. Here, we report evidence of aggregated BOULE formations, another DAZ family protein, during sperm development. Data suggest that in mouse testis, BOULE forms SDS-resistant amyloid-like aggregates. BOULE aggregate formation correlates with dynamic developmental expression during spermatogenesis but disappeared in Boule knockout testis. We also mapped essential small region in vitro BOULE aggregations, immediately downstream DAZ repeats, and found that aggregations positively correlated with temperature. We also performed enhanced UV cross-linking immunoprecipitation on BOULE aggregates from mouse testes and found that aggregates bind with a large number of spermatogenesis-related mRNAs. These findings provide insight into the amyloidogenic properties of gametogenesis-specific RNA binding proteins as a conserved feature in mammalian reproduction. Further investigation is warranted to understand the functional significance of BOULE amyloid-like formation during mouse spermatogenesis.

     

  • CLC number: R321.1, Document code: A
    The authors reported no conflict of interests.
  • loading
  • [1]
    Berchowitz LE, Kabachinski G, Walker MR, et al. Regulated formation of an amyloid-like translational repressor governs gametogenesis[J]. Cell, 2015, 163(2): 406–418. doi: 10.1016/j.cell.2015.08.060
    [2]
    Carpenter K, Bell RB, Yunus J, et al. Phosphorylation-mediated clearance of amyloid-like assemblies in meiosis[J]. Dev Cell, 2018, 45(3): 392–405.e6. doi: 10.1016/j.devcel.2018.04.001
    [3]
    Fowler DM, Koulov AV, Alory-Jost C, et al. Functional amyloid formation within mammalian tissue[J]. PLoS Biol, 2006, 4(1): e6. doi: 10.1371/journal.pbio.0040006
    [4]
    Hewetson A, Do HQ, Myers C, et al. Functional amyloids in reproduction[J]. Biomolecules, 2017, 7(3): 46. doi: 10.3390/biom7030046
    [5]
    Hewetson A, Khan NH, Dominguez MJ, et al. Maturation of the functional mouse CRES amyloid from globular form[J]. Proc Natl Acad Sci U S A, 2020, 117(28): 16363–16372. doi: 10.1073/pnas.2006887117
    [6]
    Nott TJ, Petsalaki E, Farber P, et al. Phase transition of a disordered nuage protein generates environmentally responsive membraneless organelles[J]. Mol Cell, 2015, 57(5): 936–947. doi: 10.1016/j.molcel.2015.01.013
    [7]
    Shin Y, Brangwynne CP. Liquid phase condensation in cell physiology and disease[J]. Science, 2017, 357(6357): eaaf4382. doi: 10.1126/science.aaf4382
    [8]
    Matzuk MM, Burns KH. Genetics of mammalian reproduction: modeling the end of the germline[J]. Annu Rev Physiol, 2012, 74: 503–528. doi: 10.1146/annurev-physiol-020911-153248
    [9]
    Alberti S, Halfmann R, King O, et al. A systematic survey identifies prions and illuminates sequence features of prionogenic proteins[J]. Cell, 2009, 137(1): 146–158. doi: 10.1016/j.cell.2009.02.044
    [10]
    Shah C, VanGompel MJM, Naeem V, et al. Widespread presence of human BOULE homologs among animals and conservation of their ancient reproductive function[J]. PLoS Genet, 2010, 6(7): e1001022. doi: 10.1371/journal.pgen.1001022
    [11]
    Xu EY, Moore FL, Pera RAR. A gene family required for human germ cell development evolved from an ancient meiotic gene conserved in metazoans[J]. Proc Natl Acad Sci U S A, 2001, 98(13): 7414–7419. doi: 10.1073/pnas.131090498
    [12]
    VanGompel MJW, Xu EY. The roles of the DAZ family in spermatogenesis: more than just translation?[J]. Spermatogenesis, 2011, 1(1): 36–46. doi: 10.4161/spmg.1.1.14659
    [13]
    Couthouis J, Hart MP, Shorter J, et al. A yeast functional screen predicts new candidate ALS disease genes[J]. Proc Natl Acad Sci U S A, 2011, 108(52): 20881–20890. doi: 10.1073/pnas.1109434108
    [14]
    King OD, Gitler AD, Shorter J. The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease[J]. Brain Res, 2012, 1462: 61–80. doi: 10.1016/j.brainres.2012.01.016
    [15]
    Xu EY, Lee DF, Klebes A, et al. Human BOULE gene rescues meiotic defects in infertile flies[J]. Hum Mol Genet, 2003, 12(2): 169–175. doi: 10.1093/hmg/ddg017
    [16]
    VanGompel MJW, Xu EY. A novel requirement in mammalian spermatid differentiation for the DAZ-family protein Boule[J]. Hum Mol Genet, 2010, 19(12): 2360–2369. doi: 10.1093/hmg/ddq109
    [17]
    Bellvé AR. Purification, culture, and fractionation of spermatogenic cells[J]. Methods Enzymol, 1993, 225: 84–113. doi: 10.1016/0076-6879(93)25009-q
    [18]
    Halfmann R, Lindquist S. Screening for amyloid aggregation by semi-denaturing detergent-agarose gel electrophoresis[J]. J Vis Exp, 2008, (17): 838. doi: 10.3791/838
    [19]
    Ji S, Luo Y, Cai Q, et al. LC domain-mediated coalescence is essential for otu enzymatic activity to extend Drosophila lifespan[J]. Mol Cell, 2019, 74(2): 363–377.e5. doi: 10.1016/j.molcel.2019.02.004
    [20]
    Van Nostrand EL, Pratt GA, Shishkin AA, et al. Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP)[J]. Nat Methods, 2016, 13(6): 508–514. doi: 10.1038/nmeth.3810
    [21]
    Bagriantsev SN, Kushnirov VV, Liebman SW. Analysis of amyloid aggregates using agarose gel electrophoresis[J]. Methods Enzymol, 2006, 412: 33–48. doi: 10.1016/S0076-6879(06)12003-0
    [22]
    Berchowitz LE, Gajadhar AS, van Werven FJ, et al. A developmentally regulated translational control pathway establishes the meiotic chromosome segregation pattern[J]. Genes Dev, 2013, 27(19): 2147–2163. doi: 10.1101/gad.224253.113
    [23]
    Adiutori R, Aarum J, Zubiri I, et al. The proteome of neurofilament-containing protein aggregates in blood[J]. Biochem Biophys Rep, 2018, 14: 168–177. doi: 10.1016/j.bbrep.2018.04.010
    [24]
    Pani I, Madhu P, Najiya N, et al. Differentiating conformationally distinct Alzheimer's amyloid-β oligomers using liquid crystals[J]. J Phys Chem Lett, 2020, 11(21): 9012–9018. doi: 10.1021/acs.jpclett.0c01867
    [25]
    Molliex A, Temirov J, Lee J, et al. Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization[J]. Cell, 2015, 163(1): 123–133. doi: 10.1016/j.cell.2015.09.015
    [26]
    Pak CW, Kosno M, Holehouse AS, et al. Sequence determinants of intracellular phase separation by complex coacervation of a disordered protein[J]. Mol Cell, 2016, 63(1): 72–85. doi: 10.1016/j.molcel.2016.05.042
    [27]
    Kim B, Cooke HJ, Rhee K. DAZL is essential for stress granule formation implicated in germ cell survival upon heat stress[J]. Development, 2012, 139(3): 568–578. doi: 10.1242/dev.075846
    [28]
    Van Nostrand EL, Freese P, Pratt GA, et al. A large-scale binding and functional map of human RNA-binding proteins[J]. Nature, 2020, 583(7818): 711–719. doi: 10.1038/s41586-020-2077-3
    [29]
    Protter DSW, Parker R. Principles and properties of stress granules[J]. Trends Cell Biol, 2016, 26(9): 668–679. doi: 10.1016/j.tcb.2016.05.004
    [30]
    Youn JY, Dyakov BJA, Zhang J, et al. Properties of stress granule and P-body proteomes[J]. Mol Cell, 2019, 76(2): 286–294. doi: 10.1016/j.molcel.2019.09.014
    [31]
    Lin Y, Protter DSW, Rosen MK, et al. Formation and maturation of phase-separated liquid droplets by RNA-binding proteins[J]. Mol Cell, 2015, 60(2): 208–219. doi: 10.1016/j.molcel.2015.08.018
    [32]
    Kato M, Han TW, Xie S, et al. Cell-free formation of RNA granules: low complexity sequence domains form dynamic fibers within hydrogels[J]. Cell, 2012, 149(4): 753–767. doi: 10.1016/j.cell.2012.04.017
    [33]
    Vaquer-Alicea J, Diamond MI. Propagation of protein aggregation in neurodegenerative diseases[J]. Annu Rev Biochem, 2019, 88: 785–810. doi: 10.1146/annurev-biochem-061516-045049
    [34]
    Kayed R, Head E, Thompson JL, et al. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis[J]. Science, 2003, 300(5618): 486–489. doi: 10.1126/science.1079469
    [35]
    Boke E, Ruer M, Wühr M, et al. Amyloid-like self-assembly of a cellular compartment[J]. Cell, 2016, 166(3): 637–650. doi: 10.1016/j.cell.2016.06.051
  • JBR-2022-0072-supplementary.pdf
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(7)

    Article Metrics

    Article views (280) PDF downloads(34) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return