Discovery of novel isoforms of Huntingtin reveals a new hominid-specific exon

PLoS ONE

Volumn 10, Issue 5, 2015, Pages

  Ruzo, Albert ^a   Ismailoglu, Ismail ^a   Popowski, Melissa ^a   Haremaki, Tomomi ^a   Croft, Gist F ^a   Deglincerti, Alessia ^a   Brivanlou, Ali H ^a  

^a ROCKEFELLER UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HUNTINGTIN; HTT PROTEIN, HUMAN; HTT PROTEIN, MOUSE; ISOPROTEIN; MESSENGER RNA; NERVE PROTEIN; NUCLEAR PROTEIN;

3' UNTRANSLATED REGION; ANIMAL TISSUE; ARTICLE; BRAIN CELL; CELL DIFFERENTIATION; CONTROLLED STUDY; EMBRYO; EMBRYONIC STEM CELL; EXON; FEMALE; GENE EXPRESSION; GENE IDENTIFICATION; GENE LOCATION; GENETIC TRANSCRIPTION; GENETIC VARIABILITY; HOMINID; HTT GENE; HUMAN; HUMAN CELL; NONHUMAN; OPEN READING FRAME; POLYMERASE CHAIN REACTION; QUANTITATIVE ANALYSIS; RNA SEQUENCE; RNA SPLICING; SEQUENCE ALIGNMENT; ANIMAL; GENETICS; HUMAN EMBRYONIC STEM CELL; HUNTINGTON CHOREA; KNOCKOUT MOUSE; METABOLISM; MOUSE; PATHOLOGY; SPECIES DIFFERENCE;

ANIMALS; EXONS; HUMAN EMBRYONIC STEM CELLS; HUMANS; HUNTINGTIN PROTEIN; HUNTINGTON DISEASE; MICE; MICE, KNOCKOUT; NERVE TISSUE PROTEINS; NUCLEAR PROTEINS; PROTEIN ISOFORMS; RNA, MESSENGER; SPECIES SPECIFICITY;

EID: 84949522958     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0127687     Document Type: Article

References (29)

1. Wu C, Orozco C, Boyer J, Leglise M, Goodale J, Batalov S, et al. (2009) BioGPS: an extensible and customizable portal for querying and organizing gene annotation resources. Genome Biol 10:R130. doi: 10.1186/gb-2009-10-11-r130 PMID: 19919682
2. Wu C, Macleod I, Su AI (2013) BioGPS and MyGene.info: organizing online, gene-centric information. Nucleic Acids Res 41:D561-D565. doi: 10.1093/nar/gks1114 PMID: 23175613
3. Woda JM, Calzonetti T, Hilditch-Maguire P, Duyao MP, Conlon RA, MacDonald ME (2005) Inactivation of the Huntington's disease gene (Hdh) impairs anterior streak formation and early patterning of the mouse embryo. BMC DevBiol 5:17. doi: 10.1186/1471-213X-5-17 PMID: 16109169
4. Zeitlin S, Liu JP, Chapman DL, Papaioannou VE, Efstratiadis A (1995) Increased apoptosis and early embryonic lethality in mice nullizygousforthe Huntington's disease gene homologue. Nat Genet 11:155-163. doi: 10.1038/ng1095-155 PMID: 7550343
5. Dragatsis I, Efstratiadis A, Zeitlin S (1998) Mouse mutant embryos lacking huntingtin are rescued from lethality by wild-type extraembryonic tissues. Development 125:1529-1539. PMID: 9502734
6. Menalled LB (2005) Knock-in mouse models of Huntington's disease. NeuroRx 2:465-470. doi: 10. 1602/neurorx.2.3.465 PMID: 16389309
7. Menalled LB, Chesselet M-F (2002) Mouse models of Huntington's disease. Trends Pharmacol Sci 23:32-39. PMID: 11804649
8. Ross CA, Tabrizi SJ (2011) Huntington's disease: from molecular pathogenesis to clinical treatment. Lancet Neurol 10:83-98. doi: 10.1016/S1474-4422 (10) 70245-3 PMID: 21163446
9. Lin B, Nasir J, MacDonald H, Hutchinson G, Graham RK, Romens JM, et al. (1994) Sequence of the murine Huntington disease gene: evidence for conservation, alternate splicing and polymorphism in a triplet (CCG) repeat [corrected]. Human Molecular Genetics 3:85-92. PMID: 8162057
10. Hughes AC, Mort M, Elliston L, Thomas RM, Brooks SP, Dunnett SB, et al. (2014) Identification of novel alternative splicing events in the huntingtin gene and assessment of the functional consequences using structural protein homology modelling. J Mol Biol 426:1428-1438. doi: 10.1016/j.jmb.2013.12. 028 PMID: 24389360
11. Sathasivam K, Neueder A, Gipson TA, Landles C, Benjamin AC, Bondulich MK, et al. (2013) Aberrant splicing of HTT generates the pathogenic exon 1 protein in Huntington disease. Proc Natl Acad Sci USA 110:2366-2370. doi: 10.1073/pnas.1221891110 PMID: 23341618
12. Feyeux M, Bourgois-Rocha F, Redfern A, Giles P, Lefort N, Aubert S, et al. (2012) Early transcriptional changes linked to naturally occurring Huntington's disease mutations in neural derivatives of human embryonic stem cells. Human Molecular Genetics 21:3883-3895. doi: 10.1093/hmg/dds216 PMID: 22678061
13. James D, Noggle SA, Swigut T, Brivanlou AH (2006) Contribution of human embryonic stem cells to mouse blastocysts. Dev Biol 295:90-102. doi: 10.1016/j.ydbio.2006.03.026 PMID: 16769046
14. Rosa A, Spagnoli FM, Brivanlou AH (2009) The miR-430/427/302 family controls mesendodermal fate specification via species-specific target selection. Dev Cell 16:517-527. doi: 10.1016/j.devcel.2009. 02.007 PMID: 19386261
15. Bradley CK, Scott HA, Chami O, Peura TT, Dumevska B, Schmidt U, et al. (2011) Derivation of Huntington's disease-affected human embryonic stem cell lines. Stem Cells Dev 20:495-502. doi: 10.1089/scd.2010.0120 PMID: 20649476
16. Desmond CR, Atwal RS, Xia J, Truant R (2012) Identification of a karyopherin (51/(52 proline-tyrosine nuclear localization signal in huntingtin protein. J Biol Chem 287:39626-39633. doi: 10.1074/jbc. M112.412379 PMID: 23012356
17. Atwal RS, Xia J, Pinchev D, Taylor J, Epand RM, Truant R. (2007) Huntingtin has a membrane association signal that can modulate huntingtin aggregation, nuclear entry and toxicity. Human Molecular Genetics 16:2600-2615. doi: 10.1093/hmg/ddm217 PMID: 17704510
18. Atwal RS, Truant R (2008) A stress sensitive ER membrane-association domain in Huntingtin protein defines a potential role for Huntingtin in the regulation of autophagy. Autophagy 4:91-93. PMID: 17986868
19. Maiuri T, Woloshansky T, Xia J, Truant R (2013) The huntingtin N17 domain is a multifunctional CRM1 and Ran-dependent nuclear and cilial export signal. Human Molecular Genetics 22:1383-1394. doi: 10.1093/hmg/dds554 PMID: 23297360
20. Xia J, Lee DH, Taylor J, Vandelft M, Truant R (2003) Huntingtin contains a highly conserved nuclear export signal. Human Molecular Genetics 12:1393-1403. PMID: 12783847
21. Luo S, Vacher C, Davies JE, Rubinsztein DC (2005) Cdk5 phosphorylation of huntingtin reduces its cleavage by caspases: implications for mutant huntingtin toxicity. J Cell Biol 169:647-656. doi: 10. 1083/jcb.200412071 PMID: 15911879
22. Wellington CL, Ellerby LM, Gutekunst C-A, Rogers D, Warby S, Graham RK, et al. (2002) Caspase cleavage of mutant huntingtin precedes neurodegeneration in Huntington's disease. J Neurosci 22:7862-7872. PMID: 12223539
23. Hermel E, Gafni J, Propp SS, Leavitt BR, Wellington CL, Young JE, et al. (2004) Specific caspase interactions and amplification are involved in selective neuronal vulnerability in Huntington's disease. Cell Death Differ 11:424-438. doi: 10.1038/sj.cdd.4401358 PMID: 14713958
24. Sawa A, Nagata E, Sutcliffe S, Dulloor P, Cascio MB, Ozeki Y, et al. (2005) Huntingtin is cleaved by caspases in the cytoplasm and translocated to the nucleus via perinuclear sites in Huntington's disease patient lymphoblasts. Neurobiology of Disease 20:267-274. doi: 10.1016/j.nbd.2005.02.013 PMID: 15890517
25. Wellington CL, Singaraja R, Ellerby L, Savill J, Roy S, Leavitt B, et al. (2000) Inhibiting caspase cleavage of huntingtin reduces toxicity and aggregate formation in neuronal andnonneuronal cells. J Biol Chem 275:19831-19838. doi: 10.1074/jbc. M001475200 PMID: 10770929
26. Wu JQ, Habegger L, Noisa P, Szekely A, Qiu C, Hutchison S, et al. (2010) Dynamictranscriptomes during neural differentiation of human embryonic stem cells revealed by short, long, and paired-end sequencing. Proc Natl Acad Sci USA 107:5254-5259. doi: 10.1073/pnas.0914114107 PMID: 20194744
27. Gill BJ, Pisapia DJ, Malone HR, Goldstein H, Lei L, Sonabend A, et al. (2014) MRI-localized biopsies reveal subtype-specific differences in molecular and cellular composition at the margins of glioblastoma. Proc Natl Acad Sci USA 111:12550-12555. doi: 10.1073/pnas.1405839111 PMID: 25114226
28. Shi Y, Kirwan P, Smith J, Robinson HPC, Livesey FJ (2012) Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses. Nat Neurosci 15:477-86-S1. doi: 10.1038/nn. 3041
29. Trapnell C, Roberts A, Goff L, Pertea G, Kim D, Kelley DR, et al. (2012) Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc 7:562-578. doi: 10.1038/nprot.2012.016 PMID: 22383036