PTBP1 and PTBP2 Serve Both Specific and Redundant Functions in Neuronal Pre-mRNA Splicing

Cell Reports

Volumn 17, Issue 10, 2016, Pages 2766-2775

  Vuong, John K ^a   Lin, Chia Ho ^b   Zhang, Min ^a   Chen, Liang ^c   Black, Douglas L ^b   Zheng, Sika ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

alternative splicing; brain development; CLIP; GeneSplice; neuronal differentiation; PTBP1; PTBP2; RNA binding proteins; RNA seq; splicing reprogramming

Indexed keywords

MESSENGER RNA; POLYPYRIMIDINE TRACT BINDING PROTEIN; POLYPYRIMIDINE TRACT BINDING PROTEIN 1; POLYPYRIMIDINE TRACT BINDING PROTEIN 2; TRANSCRIPTOME; UNCLASSIFIED DRUG; HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN; NERVE PROTEIN; PTBP1 PROTEIN, MOUSE; PTBP2 PROTEIN, MOUSE; RNA PRECURSOR;

ALLELE; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BRAIN DEVELOPMENT; CONTROLLED STUDY; EXON; FOREBRAIN; IN VIVO STUDY; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN RNA BINDING; RNA SPLICING; TRANSGENE; ALTERNATIVE RNA SPLICING; ANIMAL; BRAIN; GENE EXPRESSION REGULATION; GENE TARGETING; GENETICS; KNOCKOUT MOUSE; METABOLISM; NERVE CELL;

ALTERNATIVE SPLICING; ANIMALS; BRAIN; GENE EXPRESSION REGULATION; GENE KNOCK-IN TECHNIQUES; HETEROGENEOUS-NUCLEAR RIBONUCLEOPROTEINS; MICE; MICE, KNOCKOUT; NERVE TISSUE PROTEINS; NEURONS; POLYPYRIMIDINE TRACT-BINDING PROTEIN; RNA PRECURSORS; RNA SPLICING;

EID: 85002748606     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2016.11.034     Document Type: Article

References (31)

1. Amir-Ahmady, B., Boutz, P.L., Markovtsov, V., Phillips, M.L., Black, D.L., Exon repression by polypyrimidine tract binding protein. RNA 11 (2005), 699–716.
2. Boutz, P.L., Stoilov, P., Li, Q., Lin, C.-H., Chawla, G., Ostrow, K., Shiue, L., Ares, M. Jr., Black, D.L., A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes Dev. 21 (2007), 1636–1652.
3. Chen, L., Zheng, S., Identify alternative splicing events based on position-specific evolutionary conservation. PLoS ONE, 3, 2008, e2806.
4. Damianov, A., Ying, Y., Lin, C.-H., Lee, J.-A., Tran, D., Vashisht, A.A., Bahrami-Samani, E., Xing, Y., Martin, K.C., Wohlschlegel, J.A., Black, D.L., Rbfox proteins regulate splicing as part of a large multiprotein complex LASR. Cell 165 (2016), 606–619.
5. Dixon, J.R., Jung, I., Selvaraj, S., Shen, Y., Antosiewicz-Bourget, J.E., Lee, A.Y., Ye, Z., Kim, A., Rajagopal, N., Xie, W., et al. Chromatin architecture reorganization during stem cell differentiation. Nature 518 (2015), 331–336.
6. Han, A., Stoilov, P., Linares, A.J., Zhou, Y., Fu, X.-D., Black, D.L., De novo prediction of PTBP1 binding and splicing targets reveals unexpected features of its RNA recognition and function. PLoS Comput. Biol., 10, 2014, e1003442.
7. Keppetipola, N., Sharma, S., Li, Q., Black, D.L., Neuronal regulation of pre-mRNA splicing by polypyrimidine tract binding proteins, PTBP1 and PTBP2. Crit. Rev. Biochem. Mol. Biol. 47 (2012), 360–378.
8. Keppetipola, N.M., Yeom, K.-H., Hernandez, A.L., Bui, T., Sharma, S., Black, D.L., Multiple determinants of splicing repression activity in the polypyrimidine tract binding proteins, PTBP1 and PTBP2. RNA 22 (2016), 1172–1180.
9. König, J., Zarnack, K., Rot, G., Curk, T., Kayikci, M., Zupan, B., Turner, D.J., Luscombe, N.M., Ule, J., iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution. Nat. Struct. Mol. Biol. 17 (2010), 909–915.
10. Lambert, N., Robertson, A., Jangi, M., McGeary, S., Sharp, P.A., Burge, C.B., RNA Bind-n-Seq: quantitative assessment of the sequence and structural binding specificity of RNA binding proteins. Mol. Cell 54 (2014), 887–900.
11. Li, Q., Zheng, S., Han, A., Lin, C.-H., Stoilov, P., Fu, X.-D., Black, D.L., The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation. eLife, 3, 2014, e01201.
12. Licatalosi, D.D., Mele, A., Fak, J.J., Ule, J., Kayikci, M., Chi, S.W., Clark, T.A., Schweitzer, A.C., Blume, J.E., Wang, X., et al. HITS-CLIP yields genome-wide insights into brain alternative RNA processing. Nature 456 (2008), 464–469.
13. Licatalosi, D.D., Yano, M., Fak, J.J., Mele, A., Grabinski, S.E., Zhang, C., Darnell, R.B., Ptbp2 represses adult-specific splicing to regulate the generation of neuronal precursors in the embryonic brain. Genes Dev. 26 (2012), 1626–1642.
14. Linares, A.J., Lin, C.-H., Damianov, A., Adams, K.L., Novitch, B.G., Black, D.L., The splicing regulator PTBP1 controls the activity of the transcription factor Pbx1 during neuronal differentiation. eLife, 4, 2015, e09268.
15. Luco, R.F., Pan, Q., Tominaga, K., Blencowe, B.J., Pereira-Smith, O.M., Misteli, T., Regulation of alternative splicing by histone modifications. Science 327 (2010), 996–1000.
16. Makeyev, E.V., Zhang, J., Carrasco, M.A., Maniatis, T., The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol. Cell 27 (2007), 435–448.
17. Pan, Q., Shai, O., Lee, L.J., Frey, B.J., Blencowe, B.J., Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat. Genet. 40 (2008), 1413–1415.
18. Raj, B., Blencowe, B.J., Alternative splicing in the mammalian nervous system: recent insights into mechanisms and functional roles. Neuron 87 (2015), 14–27.
19. Raj, B., Irimia, M., Braunschweig, U., Sterne-Weiler, T., O'Hanlon, D., Lin, Z.-Y., Chen, G.I., Easton, L.E., Ule, J., Gingras, A.-C., et al. A global regulatory mechanism for activating an exon network required for neurogenesis. Mol. Cell 56 (2014), 90–103.
20. Spellman, R., Llorian, M., Smith, C.W.J., Crossregulation and functional redundancy between the splicing regulator PTB and its paralogs nPTB and ROD1. Mol. Cell 27 (2007), 420–434.
21. Srinivas, S., Watanabe, T., Lin, C.S., William, C.M., Tanabe, Y., Jessell, T.M., Costantini, F., Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus. BMC Dev. Biol., 1, 2001, 4.
22. Stork, C., Zheng, S., Genome-wide profiling of RNA-protein interactions using CLIP-seq. Methods Mol. Biol. 1421 (2016), 137–151.
23. Vuong, C.K., Black, D.L., Zheng, S., The neurogenetics of alternative splicing. Nat. Rev. Neurosci. 17 (2016), 265–281.
24. Wang, E.T., Sandberg, R., Luo, S., Khrebtukova, I., Zhang, L., Mayr, C., Kingsmore, S.F., Schroth, G.P., Burge, C.B., Alternative isoform regulation in human tissue transcriptomes. Nature 456 (2008), 470–476.
25. Xue, Y., Ouyang, K., Huang, J., Zhou, Y., Ouyang, H., Li, H., Wang, G., Wu, Q., Wei, C., Bi, Y., et al. Direct conversion of fibroblasts to neurons by reprogramming PTB-regulated microRNA circuits. Cell 152 (2013), 82–96.
26. Yeo, G.W., Coufal, N.G., Liang, T.Y., Peng, G.E., Fu, X.-D., Gage, F.H., An RNA code for the FOX2 splicing regulator revealed by mapping RNA-protein interactions in stem cells. Nat. Struct. Mol. Biol. 16 (2009), 130–137.
27. Zambrowicz, B.P., Imamoto, A., Fiering, S., Herzenberg, L.A., Kerr, W.G., Soriano, P., Disruption of overlapping transcripts in the ROSA beta geo 26 gene trap strain leads to widespread expression of beta-galactosidase in mouse embryos and hematopoietic cells. Proc. Natl. Acad. Sci. USA 94 (1997), 3789–3794.
28. Zhang, X., Chen, M.H., Wu, X., Kodani, A., Fan, J., Doan, R., Ozawa, M., Ma, J., Yoshida, N., Reiter, J.F., et al. Cell-type-specific alternative splicing governs cell fate in the developing cerebral cortex. Cell 166 (2016), 1147–1162.e15.
29. Zheng, S., Alternative splicing and nonsense-mediated mRNA decay enforce neural specific gene expression. Int. J. Dev. Neurosci., 2016, 10.1016/j.ijdevneu.2016.03.003.
30. Zheng, S., Eacker, S.M., Hong, S.J., Gronostajski, R.M., Dawson, T.M., Dawson, V.L., NMDA-induced neuronal survival is mediated through nuclear factor I-A in mice. J. Clin. Invest. 120 (2010), 2446–2456.
31. Zheng, S., Gray, E.E., Chawla, G., Porse, B.T., O'Dell, T.J., Black, D.L., PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2. Nat. Neurosci. 15 (2012), 381–388 S1.