The splicing regulators Esrp1 and Esrp2 direct an epithelial splicing program essential for mammalian development

eLife

Volumn 4, Issue September2015, 2015, Pages

  Bebee, Thomas W ^a   Park, Juw Won ^b,c   Sheridan, Katherine I ^a   Warzecha, Claude C ^a   Cieply, Benjamin W ^a   Rohacek, Alex M ^a   Xing, Yi ^b   Carstens, Russ P ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c University of Louisville   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EPITHELIAL SPLICING REGULATORY PROTEIN 1; EPITHELIAL SPLICING REGULATORY PROTEIN 2; REGULATOR PROTEIN; UNCLASSIFIED DRUG; ESRP1 PROTEIN, MOUSE; ESRP2 PROTEIN, MOUSE; RNA BINDING PROTEIN;

ALTERNATIVE RNA SPLICING; ANIMAL CELL; ARTICLE; CELL CULTURE; CELL MATURATION; EMBRYO; EPITHELIUM CELL; GENE EXPRESSION; GENE ONTOLOGY; IN SITU HYBRIDIZATION; MOUSE; NONHUMAN; ORGANOGENESIS; PHENOTYPE; PHYLOGENY; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; WESTERN BLOTTING; ANIMAL; ANIMAL STRUCTURES; BAGG ALBINO MOUSE; C57BL MOUSE; EMBRYOLOGY; FEMALE; GENE DELETION; GENE EXPRESSION PROFILING; GENETICS; MALE; METABOLISM; PHYSIOLOGY;

ANIMAL STRUCTURES; ANIMALS; EPITHELIAL CELLS; FEMALE; GENE DELETION; GENE EXPRESSION PROFILING; MALE; MICE, INBRED BALB C; MICE, INBRED C57BL; RNA-BINDING PROTEINS;

EID: 84942063845     PISSN: None     EISSN: 2050084X     Source Type: Journal    
DOI: 10.7554/eLife.08954     Document Type: Article

References (75)

1. Anderson ES, Lin CH, Xiao X, Stoilov P, Burge CB, Black DL. 2012. The cardiotonic steroid digitoxin regulates alternative splicing through depletion of the splicing factors SRSF3 and TRA2B. RNA 18: 1041-1049. doi: 10. 1261/rna. 032912. 112.
2. Andl T, Ahn K, Kairo A, Chu EY, Wine-Lee L, Reddy ST, Croft NJ, Cebra-Thomas JA, Metzger D, Chambon P, Lyons KM, Mishina Y, Seykora JT, Crenshaw EB III, Millar SE. 2004. Epithelial Bmpr1a regulates differentiation and proliferation in postnatal hair follicles and is essential for tooth development. Development 131: 2257-2268. doi: 10. 1242/dev. 01125.
3. Barberan-Soler S, Zahler AM. 2008. Alternative splicing regulation during C. elegans development: splicing factors as regulated targets. PLOS Genetics 4: e1000001. doi: 10. 1371/journal. pgen. 1000001.
4. Brown RL, Reinke LM, Damerow MS, Perez D, Chodosh LA, Yang J, Cheng C. 2011. CD44 splice isoform switching in human and mouse epithelium is essential for epithelial-mesenchymal transition and breast cancer progression. The Journal of Clinical Investigation 121: 1064-1074. doi: 10. 1172/JCI44540.
5. Carstens RP, Wagner EJ, Garcia-Blanco MA. 2000. An intronic splicing silencer causes skipping of the IIIb exon of fibroblast growth factor receptor 2 through involvement of polypyrimidine tract binding protein. Molecular and Cellular Biology 20: 7388-7400. doi: 10. 1128/MCB. 20. 19. 7388-7400. 2000.
6. Castle JC, Zhang C, Shah JK, Kulkarni AV, Kalsotra A, Cooper TA, Johnson JM. 2008. Expression of 24, 426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines. Nature Genetics 40: 1416-1425. doi: 10. 1038/ng. 264.
7. Chen M, Manley JL. 2009. Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches. Nature Reviews. Molecular Cell Biology 10: 741-754. doi: 10. 1038/nrm2777.
8. Cieply B, Carstens RP. 2015. Functional roles of alternative splicing factors in human disease. Wiley Interdisciplinary Reviews. RNA 6: 311-326. doi: 10. 1002/wrna. 1276.
9. De Moerlooze L, Spencer-Dene B, Revest J, Hajihosseini M, Rosewell I, Dickson C. 2000. An important role for the IIIb isoform of fibroblast growth factor receptor 2 (FGFR2) in mesenchymal-epithelial signalling during mouse organogenesis. Development 127: 483-492.
10. Dittmar KA, Jiang P, Park JW, Amirikian K, Wan J, Shen S, Xing Y, Carstens RP. 2012. Genome-wide determination of a broad esrp-regulated posttranscriptional network by high-throughput sequencing. Molecular and Cellular Biology 32: 1468-1482. doi: 10. 1128/MCB. 06536-11.
11. Dixon MJ, Marazita ML, Beaty TH, Murray JC. 2011. Cleft lip and palate: understanding genetic and environmental influences. Nature Reviews. Genetics 12: 167-178. doi: 10. 1038/nrg2933.
12. Fu XD, Ares M Jr. 2014. Context-dependent control of alternative splicing by RNA-binding proteins. Nature Reviews. Genetics 15: 689-701. doi: 10. 1038/nrg3778.
13. Fuchs E. 2007. Scratching the surface of skin development. Nature 445: 834-842. doi: 10. 1038/nature05659.
14. Gehman LT, Stoilov P, Maguire J, Damianov A, Lin CH, Shiue L, Ares M Jr, Mody I, Black DL. 2011. The splicing regulator Rbfox1 (A2BP1) controls neuronal excitation in the mammalian brain. Nature Genetics 43: 706-711. doi: 10. 1038/ng. 841.
15. Gladden AB, Hebert AM, Schneeberger EE, McClatchey AI. 2010. The NF2 tumor suppressor, Merlin, regulates epidermal development through the establishment of a junctional polarity complex. Developmental Cell 19: 727-739. doi: 10. 1016/j. devcel. 2010. 10. 008.
16. Graveley BR. 2001. Alternative splicing: increasing diversity in the proteomic world. Trends in Genetics 17: 100-107. doi: 10. 1016/S0168-9525(00)02176-4.
17. Greco V, Chen T, RendlM, SchoberM, Pasolli HA, Stokes N, Dela Cruz-Racelis J, Fuchs E. 2009. A two-step mechanism for stem cell activation during hair regeneration. Cell Stem Cell 4: 155-169. doi: 10. 1016/j. stem. 2008. 12. 009.
18. Han H, Irimia M, Ross PJ, Sung HK, Alipanahi B, David L, Golipour A, Gabut M, Michael IP, Nachman EN, Wang E, Trcka D, Thompson T, O'Hanlon D, Slobodeniuc V, Barbosa-Morais NL, Burge CB, Moffat J, Frey BJ, Nagy A, Ellis J, Wrana JL, Blencowe BJ. 2013. MBNL proteins repress ES-cell-specific alternative splicing and reprogramming. Nature 498: 241-245. doi: 10. 1038/nature12270.
19. Hovhannisyan RH, Carstens RP. 2005. A novel intronic cis element, ISE/ISS-3, regulates rat fibroblast growth factor receptor 2 splicing through activation of an upstream exon and repression of a downstream exon containing a noncanonical branch point sequence. Molecular and Cellular Biology 25: 250-263. doi: 10. 1128/MCB. 25. 1. 250-263. 2005.
20. Huang da W, Sherman BT, Lempicki RA. 2009. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nature Protocols 4: 44-57. doi: 10. 1038/nprot. 2008. 211.
21. Juriloff DM, Harris MJ. 2008. Mouse genetic models of cleft lip with or without cleft palate. Birth Defects Research Part A, Clinical and Molecular Teratology 82: 63-77. doi: 10. 1002/bdra. 20430.
22. Kalsotra A, Cooper TA. 2011. Functional consequences of developmentally regulated alternative splicing. Nature Reviews. Genetics 12: 715-729. doi: 10. 1038/nrg3052.
23. Kalsotra A, Xiao X, Ward AJ, Castle JC, Johnson JM, Burge CB, Cooper TA. 2008. A postnatal switch of CELF and MBNL proteins reprograms alternative splicing in the developing heart. Proceedings of the National Academy of Sciences of USA 105: 20333-20338. doi: 10. 1073/pnas. 0809045105.
24. Kelemen O, Convertini P, Zhang Z, Wen Y, Shen M, Falaleeva M, Stamm S. 2013. Function of alternative splicing. Gene 514: 1-30. doi: 10. 1016/j. gene. 2012. 07. 083.
25. Kirschner N, Haftek M, Niessen CM, Behne MJ, Furuse M, Moll I, Brandner JM. 2011. CD44 regulates tightjunction assembly and barrier function. The Journal of Investigative Dermatology 131: 932-943. doi: 10. 1038/jid. 2010. 390.
26. Koch PJ, de Viragh PA, Scharer E, Bundman D, Longley MA, Bickenbach J, Kawachi Y, Suga Y, Zhou Z, Huber M, Hohl D, Kartasova T, Jarnik M, Steven AC, Roop DR. 2000. Lessons from loricrin-deficient mice: compensatory mechanisms maintaining skin barrier function in the absence of a major cornified envelope protein. The Journal of Cell Biology 151: 389-400. doi: 10. 1083/jcb. 151. 2. 389.
27. Kypriotou M, Huber M, Hohl D. 2012. The human epidermal differentiation complex: cornified envelope precursors, S100 proteins and the 'fused genes' family. Experimental Dermatology 21: 643-649. doi: 10. 1111/j. 1600-0625. 2012. 01472. x.
28. Lee KY, Li M, Manchanda M, Batra R, Charizanis K, Mohan A, Warren SA, Chamberlain CM, Finn D, Hong H, Ashraf H, Kasahara H, Ranum LP, Swanson MS. 2013. Compound loss of muscleblind-like function in myotonic dystrophy. EMBO Molecular Medicine 5: 1887-1900. doi: 10. 1002/emmm. 201303275.
29. Li Q, Zheng S, Han A, Lin CH, Stoilov P, Fu XD, Black DL. 2014. The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation. eLife 3: e01201. doi: 10. 7554/eLife. 01201.
30. Licatalosi DD, Yano M, Fak JJ, Mele A, Grabinski SE, Zhang C, Darnell RB. 2012. Ptbp2 represses adult-specific splicing to regulate the generation of neuronal precursors in the embryonic brain. Genes & Development 26: 1626-1642. doi: 10. 1101/gad. 191338. 112.
31. Lu ZX, Huang Q, Park JW, Shen S, Lin L, Tokheim CJ, Henry MD, Xing Y. 2015. Transcriptome-wide landscape of pre-mRNA alternative splicing associated with metastatic colonization. Molecular Cancer Research 13: 305-318. doi: 10. 1158/1541-7786. MCR-14-0366.
32. Mallinjoud P, Villemin JP, Mortada H, Polay Espinoza M, Desmet FO, Samaan S, Chautard E, Tranchevent LC, Auboeuf D. 2014. Endothelial, epithelial, and fibroblast cells exhibit specific splicing programs independently of their tissue of origin. Genome Research 24: 511-521. doi: 10. 1101/gr. 162933. 113.
33. Mauger DM, Lin C, Garcia-Blanco MA. 2008. hnRNP H and hnRNP F complex with Fox2 to silence fibroblast growth factor receptor 2 exon IIIc. Molecular and Cellular Biology 28: 5403-5419. doi: 10. 1128/MCB. 00739-08.
34. Mlacki M, Darido C, Jane SM, Wilanowski T. 2014. Loss of Grainy head-like 1 is associated with disruption of the epidermal barrier and squamous cell carcinoma of the skin. PLOS ONE 9: e89247. doi: 10. 1371/journal. pone. 0089247.
35. Moroy T, Heyd F. 2007. The impact of alternative splicing in vivo: mouse models show the way. RNA 13: 1155-1171. doi: 10. 1261/rna. 554607.
36. Nissim S, Allard P, Bandyopadhyay A, Harfe BD, Tabin CJ. 2007. Characterization of a novel ectodermal signaling center regulating Tbx2 and Shh in the vertebrate limb. Developmental Biology 304: 9-21. doi: 10. 1016/j. ydbio. 2006. 12. 010.
37. Ohuchi H, Hori Y, Yamasaki M, Harada H, Sekine K, Kato S, Itoh N. 2000. FGF10 acts as a major ligand for FGF receptor 2 IIIb in mouse multi-organ development. Biochemical and Biophysical Research Communications 277: 643-649. doi: 10. 1006/bbrc. 2000. 3721.
38. Orr-Urtreger A, Bedford MT, Burakova T, Arman E, Zimmer Y, Yayon A, Givol D, Lonai P. 1993. Developmental localization of the splicing alternatives of fibroblast growth factor receptor-2 (FGFR2). Developmental Biology 158: 475-486. doi: 10. 1006/dbio. 1993. 1205.
39. Ovchinnikov D. 2009. Alcian blue/alizarin red staining of cartilage and bone in mouse. Cold Spring Harbor Protocols 2009: pdb prot5170. doi: 10. 1101/pdb. prot5170.
40. Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ. 2008. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nature Genetics 40: 1413-1415. doi: 10. 1038/ng. 259.
41. Park JW, Parisky K, Celotto AM, Reenan RA, Graveley BR. 2004. Identification of alternative splicing regulators by RNA interference in Drosophila. Proceedings of the National Academy of Sciences of USA 101: 15974-15979. doi: 10. 1073/pnas. 0407004101.
42. Patel S, Kartasova T, Segre JA. 2003. Mouse Sprr locus: a tandem array of coordinately regulated genes. Mammalian Genome 14: 140-148. doi: 10. 1007/s00335-002-2205-4.
43. Paus R, Muller-Rover S, Van Der Veen C, Maurer M, Eichmuller S, Ling G, Hofmann U, Foitzik K, Mecklenburg L, Handjiski B. 1999. A comprehensive guide for the recognition and classification of distinct stages of hair follicle morphogenesis. The Journal of Investigative Dermatology 113: 523-532. doi: 10. 1046/j. 1523-1747. 1999. 00740. x.
44. Petiot A, Conti FJ, Grose R, Revest JM, Hodivala-Dilke KM, Dickson C. 2003. A crucial role for Fgfr2-IIIb signalling in epidermal development and hair follicle patterning. Development 130: 5493-5501. doi: 10. 1242/dev. 00788.
45. Quesnel-Vallieres M, Irimia M, Cordes SP, Blencowe BJ. 2015. Essential roles for the splicing regulator nSR100/SRRM4 during nervous system development. Genes & Development 29: 746-759. doi: 10. 1101/gad. 256115. 114.
46. Ray D, Kazan H, Cook KB, Weirauch MT, Najafabadi HS, Li X, Gueroussov S, Albu M, Zheng H, Yang A, Na H, Irimia M, Matzat LH, Dale RK, Smith SA, Yarosh CA, Kelly SM, Nabet B, Mecenas D, Li W, Laishram RS, Qiao M, Lipshitz HD, Piano F, Corbett AH, Carstens RP, Frey BJ, Anderson RA, Lynch KW, Penalva LO, Lei EP, Fraser AG, Blencowe BJ, Morris QD, Hughes TR. 2013. A compendium of RNA-binding motifs for decoding gene regulation. Nature 499: 172-177. doi: 10. 1038/nature12311.
47. Rendl M, Lewis L, Fuchs E. 2005. Molecular dissection of mesenchymal-epithelial interactions in the hair follicle. PLOS Biology 3: e331. doi: 10. 1371/journal. pbio. 0030331.
48. Revest JM, Spencer-Dene B, Kerr K, De Moerlooze L, Rosewell I, Dickson C. 2001. Fibroblast growth factor receptor 2-IIIb acts upstream of Shh and Fgf4 and is required for limb bud maintenance but not for the induction of Fgf8, Fgf10, Msx1, or Bmp4. Developmental Biology 231: 47-62. doi: 10. 1006/dbio. 2000. 0144.
49. Revil T, Jerome-Majewska LA. 2013. During embryogenesis, esrp1 expression is restricted to a subset of epithelial cells and is associated with splicing of a number of developmentally important genes. Developmental Dynamics 242: 281-290. doi: 10. 1002/dvdy. 23918.
50. Rice R, Spencer-Dene B, Connor EC, Gritli-Linde A, McMahon AP, Dickson C, Thesleff I, Rice DP. 2004. Disruption of Fgf10/Fgfr2b-coordinated epithelial-mesenchymal interactions causes cleft palate. The Journal of Clinical Investigation 113: 1692-1700. doi: 10. 1172/JCI20384.
51. Saltzman AL, Pan Q, Blencowe BJ. 2011. Regulation of alternative splicing by the core spliceosomal machinery. Genes & Development 25: 373-384. doi: 10. 1101/gad. 2004811.
52. Savagner P, Valles AM, Jouanneau J, Yamada KM, Thiery JP. 1994. Alternative splicing in fibroblast growth factor receptor 2 is associated with induced epithelial-mesenchymal transition in rat bladder carcinoma cells. Molecular Biology of the Cell 5: 851-862. doi: 10. 1091/mbc. 5. 8. 851.
53. Segre JA. 2006. Epidermal barrier formation and recovery in skin disorders. The Journal of Clinical Investigation 116: 1150-1158. doi: 10. 1172/JCI28521.
54. Segre JA, Bauer C, Fuchs E. 1999. Klf4 is a transcription factor required for establishing the barrier function of the skin. Nature Genetics 22: 356-360. doi: 10. 1038/11926.
55. Shen S, Park JW, Lu ZX, Lin L, Henry MD, Wu YN, Zhou Q, Xing Y. 2014. rMATS: robust and flexible detection of differential alternative splicing from replicate RNA-Seq data. Proceedings of the National Academy of Sciences of USA 111: E5593-E5601. doi: 10. 1073/pnas. 1419161111.
56. Singh RK, Cooper TA. 2012. Pre-mRNA splicing in disease and therapeutics. Trends in Molecular Medicine 18: 472-482. doi: 10. 1016/j. molmed. 2012. 06. 006.
57. Solanas G, Benitah SA. 2013. Regenerating the skin: a task for the heterogeneous stem cell pool and surrounding niche. Nature Reviews. Molecular Cell Biology 14: 737-748. doi: 10. 1038/nrm3675.
58. Su AI, Cooke MP, Ching KA, Hakak Y, Walker JR, Wiltshire T, Orth AP, Vega RG, Sapinoso LM, Moqrich A, et al. 2002. Large-scale analysis of the human and mouse transcriptomes. Proceedings of the National Academy of Sciences of USA 99: 4465-4470. doi: 10. 1073/pnas. 012025199.
59. Thiery JP, Acloque H, Huang RY, Nieto MA. 2009. Epithelial-mesenchymal transitions in development and disease. Cell 139: 871-890. doi: 10. 1016/j. cell. 2009. 11. 007.
60. Trapnell C, Williams BA, Pertea G, Mortazavi A, Kwan G, van Baren MJ, Salzberg SL, Wold BJ, Pachter L. 2010. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nature Biotechnology 28: 511-515. doi: 10. 1038/nbt. 1621.
61. Ule J, Jensen KB, Ruggiu M, Mele A, Ule A, Darnell RB. 2003. CLIP identifies Nova-regulated RNA networks in the brain. Science 302: 1212-1215. doi: 10. 1126/science. 1090095.
62. Ule J, Ule A, Spencer J, Williams A, Hu JS, Cline M, Wang H, Clark T, Fraser C, Ruggiu M, Zeeberg BR, Kane D, Weinstein JN, Blume J, Darnell RB. 2005. Nova regulates brain-specific splicing to shape the synapse. Nature Genetics 37: 844-852. doi: 10. 1038/ng1610.
63. Vanharanta S, Marney CB, Shu W, Valiente M, Zou Y, Mele A, Darnell RB, Massague J. 2014. Loss of the multifunctional RNA-binding protein RBM47 as a source of selectable metastatic traits in breast cancer. eLife 3: e02734. doi: 10. 7554/eLife. 02734.
64. Wakabayashi-Ito N, Belvin MP, Bluestein DA, Anderson KV. 2001. Fusilli, an essential gene with a maternal role in Drosophila embryonic dorsal-ventral patterning. Developmental Biology 229: 44-54. doi: 10. 1006/dbio. 2000. 9954.
65. Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L, Mayr C, Kingsmore SF, Schroth GP, Burge CB. 2008. Alternative isoform regulation in human tissue transcriptomes. Nature 456: 470-476. doi: 10. 1038/nature07509.
66. Warzecha CC, Jiang P, Amirikian K, Dittmar KA, Lu H, Shen S, Guo W, Xing Y, Carstens RP. 2010. An ESRPregulated splicing programme is abrogated during the epithelial-mesenchymal transition. The EMBO Journal 29: 3286-3300. doi: 10. 1038/emboj. 2010. 195.
67. Warzecha CC, Sato TK, Nabet B, Hogenesch JB, Carstens RP. 2009a. ESRP1 and ESRP2 are epithelial cell-typespecific regulators of FGFR2 splicing. Molecular Cell 33: 591-601. doi: 10. 1016/j. molcel. 2009. 01. 025.
68. Warzecha CC, Shen S, Xing Y, Carstens RP. 2009b. The epithelial splicing factors ESRP1 and ESRP2 positively and negatively regulate diverse types of alternative splicing events. RNA Biology 6: 546-562. doi: 10. 4161/rna. 6. 5. 9606.
69. Wilanowski T, Caddy J, Ting SB, Hislop NR, Cerruti L, Auden A, Zhao LL, Asquith S, Ellis S, Sinclair R, Cunningham JM, Jane SM. 2008. Perturbed desmosomal cadherin expression in grainy head-like 1-null mice. The EMBO Journal 27: 886-897. doi: 10. 1038/emboj. 2008. 24.
70. Xu X, Weinstein M, Li C, Naski M, Cohen RI, Ornitz DM, Leder P, Deng C. 1998. Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction. Development 125: 753-765.
71. Xu Y, Gao XD, Lee JH, Huang H, Tan H, Ahn J, Reinke LM, Peter ME, Feng Y, Gius D, Siziopikou KP, Peng J, Xiao X, Cheng C. 2014. Cell type-restricted activity of hnRNPM promotes breast cancer metastasis via regulating alternative splicing. Genes & Development 28: 1191-1203. doi: 10. 1101/gad. 241968. 114.
72. Yang J, Hung LH, Licht T, Kostin S, Looso M, Khrameeva E, Bindereif A, Schneider A, Braun T. 2014. RBM24 is a major regulator of muscle-specific alternative splicing. Developmental Cell 31: 87-99. doi: 10. 1016/j. devcel. 2014. 08. 025.
73. Yu Z, Lin KK, Bhandari A, Spencer JA, Xu X, Wang N, Lu Z, Gill GN, Roop DR, Wertz P, Andersen B. 2006. The Grainyhead-like epithelial transactivator Get-1/Grhl3 regulates epidermal terminal differentiation and interacts functionally with LMO4. Developmental Biology 299: 122-136. doi: 10. 1016/j. ydbio. 2006. 07. 015.
74. Zhang X, Ibrahimi OA, Olsen SK, Umemori H, Mohammadi M, Ornitz DM. 2006. Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. The Journal of Biological Chemistry 281: 15694-15700. doi: 10. 1074/jbc. M601252200.
75. Zhang Y, Andl T, Yang SH, Teta M, Liu F, Seykora JT, Tobias JW, Piccolo S, Schmidt-Ullrich R, Nagy A, Taketo MM, Dlugosz AA, Millar SE. 2008. Activation of beta-catenin signaling programs embryonic epidermis to hair follicle fate. Development 135: 2161-2172. doi: 10. 1242/dev. 017459.