Abstract:
The transcription factor TCERG1 (also known as CA150) associates with RNA polymerase II holoenzyme and alters the elongation efficiency of reporter transcripts. TCERG1 is also found as a component of highly purified spliceosomes and has been implicated in splicing. To elucidate the function of TCERG1, we used short interfering RNA-mediated knockdown followed by en masse gene expression analysis to identify its cellular targets. Analysis of data from HEK293 and HeLa cells identified high confidence targets of TCERG1. We found that targets of TCERG1 were enriched in microRNA-binding sites, suggesting the possibility of post-transcriptional regulation. Consistently, reverse transcription-PCR analysis revealed that many of the changes observed upon TCERG1 knockdown were because of differences in alternative mRNA processing of the 3′-untranslated regions. Furthermore, a novel computational approach, which can identify alternatively processed events from conventional microarray data, showed that TCERG1 led to widespread alterations in mRNA processing. These findings provide the strongest support to date for a role of TCERG1 in mRNA processing and are consistent with proposals that TCERG1 couples transcription and processing. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.
Registro:
Documento: |
Artículo
|
Título: | Identification of the cellular targets of the transcription factor TCERG1 reveals a prevalent role in mrna processing |
Autor: | Pearson, J.L.; Robinson, T.J.; Muñoz, M.J.; Kornblihtt, A.R.; Garcia-Blanco, M.A. |
Filiación: | Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, United States Department of Molecular Cancer Biology, Duke University Medical Center, Durham, NC 27710, United States Medical Scientist Training Program, Duke University Medical Center, Durham, NC 27710, United States Department of Medicine, Duke University Medical Center, Durham, NC 27710, United States Center for RNA Biology, Duke University Medical Center, Durham, NC 27710, United States Laboratorio de Fisiología Y Biología Molecular, Departamento de Fisiología, Biología Molecular Y Celular, Pabellón 2, (C1428EHA) Buenos Aires, Argentina
|
Palabras clave: | Binding energy; Binding sites; Biochemistry; Gene expression; Nucleic acids; Polymers; Proteins; RNA; Targets; Transcription factors; Analysis of datums; Cellular targets; Computational approaches; Gene expression analysis; Hela cells; High confidences; Microarray datums; Pcr analysis; Reverse transcriptions; Rna polymerase ii; Short interfering rnas; Spliceosomes; Transcriptional regulations; Untranslated regions; Transcription; messenger RNA; microRNA; small interfering RNA; transcription factor; transcription factor tcerg1; unclassified drug; messenger RNA; microRNA; TCERG1 protein, human; transactivator protein; 3' untranslated region; article; binding site; cell strain HEK293; controlled study; embryo; female; gene expression; HeLa cell; human; human cell; knockout gene; microarray analysis; nucleotide sequence; priority journal; protein function; reverse transcription polymerase chain reaction; RNA processing; target cell; transcription regulation; unindexed sequence; cell line; DNA microarray; drug antagonism; gene expression profiling; genetic transcription; genetics; metabolism; physiology; RNA splicing; spliceosome; Cell Line; Gene Expression Profiling; Humans; MicroRNAs; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction; RNA Splicing; RNA, Messenger; RNA, Small Interfering; Spliceosomes; Trans-Activators; Transcription, Genetic |
Año: | 2008
|
Volumen: | 283
|
Número: | 12
|
Página de inicio: | 7949
|
Página de fin: | 7961
|
DOI: |
http://dx.doi.org/10.1074/jbc.M709402200 |
Título revista: | Journal of Biological Chemistry
|
Título revista abreviado: | J. Biol. Chem.
|
ISSN: | 00219258
|
CODEN: | JBCHA
|
CAS: | MicroRNAs; RNA, Messenger; RNA, Small Interfering; TCERG1 protein, human; Trans-Activators
|
PDF: | https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00219258_v283_n12_p7949_Pearson.pdf |
Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v283_n12_p7949_Pearson |
Referencias:
- Sune, C., Hayashi, T., Liu, Y., Lane, W.S., Young, R.A., Garcia-Blanco, M.A., (1997) Mol. Cell. Biol, 17, pp. 6029-6039
- Sune, C., Garcia-Blanco, M.A., (1995) J. Virol, 69, pp. 3098-3107
- Sune, C., Garcia-Blanco, M.A., (1999) Mol. Cell. Biol, 19, pp. 4719-4728
- Sanchez-Alvarez, M., Goldstrohm, A.C., Garcia-Blanco, M.A., Sune, C., (2006) Mol. Cell. Biol, 26, pp. 4998-5014
- Carty, S.M., Goldstrohm, A.C., Sune, C., Garcia-Blanco, M.A., Greenleaf, A.L., (2000) Proc. Natl. Acad. Sci. U. S. A, 97, pp. 9015-9020
- Goldstrohm, A.C., Albrecht, T.R., Sune, C., Bedford, M.T., Garcia-Blanco, M.A., (2001) Mol. Cell. Biol, 21, pp. 7617-7628
- Lin, K.T., Lu, R.M., Tarn, W.Y., (2004) Mol. Cell. Biol, 24, pp. 9176-9185
- Makarov, E.M., Makarova, O.V., Urlaub, H., Gentzel, M., Will, C.L., Wilm, M., Luhrmann, R., (2002) Science, 298, pp. 2205-2208
- Rappsilber, J., Ryder, U., Lamond, A.I., Mann, M., (2002) Genome Res, 12, pp. 1231-1245
- Deckert, J., Hartmuth, K., Boehringer, D., Behzadnia, N., Will, C.L., Kastner, B., Stark, H., Luhrmann, R., (2006) Mol. Cell. Biol, 26, pp. 5528-5543
- Cheng, D., Cote, J., Shaaban, S., Bedford, M.T., (2007) Mol. Cell, 25, pp. 71-83
- Kornblihtt, A.R., de la Mata, M., Fededa, J.P., Munoz, M.J., Nogues, G., (2004) RNA (N. Y.), 10, pp. 1489-1498
- Bird, G., Zorio, D.A., Bentley, D.L., (2004) Mol. Cell. Biol, 24, pp. 8963-8969
- Reed, R., (2003) Curr. Opin. Cell Biol, 15, pp. 326-331
- Goldstrohm, A.C., Greenleaf, A.L., Garcia-Blanco, M.A., (2001) Gene (Amst.), 277, pp. 31-47
- de la Mata, M., Kornblihtt, A.R., (2006) Nat. Struct. Mol. Biol, 13, pp. 973-980
- McCracken, S., Fong, N., Yankulov, K., Ballantyne, S., Pan, G., Greenblatt, J., Patterson, S.D., Bentley, D.L., (1997) Nature, 385, pp. 357-361
- Sun, X., Zhao, J., Kylberg, K., Soop, T., Palka, K., Sonnhammer, E., Visa, N., Daneholt, B., (2004) Chromosoma, 113, pp. 244-257
- Smith, M.J., Kulkarni, S., Pawson, T., (2004) Mol. Cell. Biol, 24, pp. 9274-9285
- Goldstrohm, A.C., (2001) Biochemical and Functional Analysis of the Human Transcription Factor CA150, , Ph.D. thesis, Duke University, Durham, NC
- Florez, P.M., Sessions, O.M., Wagner, E.J., Gromeier, M., Garcia-Blanco, M.A., (2005) J. Virol, 79, pp. 6172-6179
- Wagner, E.J., Garcia-Blanco, M.A., (2002) Mol. Cell, 10, pp. 943-949
- Subramanian, A., Tamayo, P., Mootha, V.K., Mukherjee, S., Ebert, B.L., Gillette, M.A., Paulovich, A., Mesirov, J.P., (2005) Proc. Natl. Acad. Sci. U. S. A, 102, pp. 15545-15550
- Cramer, P., Caceres, J.F., Cazalla, D., Kadener, S., Muro, A.F., Baralle, F.E., Kornblihtt, A.R., (1999) Mol. Cell, 4, pp. 251-258
- Fan, W., Khalid, N., Hallahan, A.R., Olson, J.M., Zhao, L.P., (2006) Theor. Biol. Med. Model, 3, p. 19
- Hu, G.K., Madore, S.J., Moldover, B., Jatkoe, T., Balaban, D., Thomas, J., Wang, Y., (2001) Genome Res, 11, pp. 1237-1245
- Cope, L.M., Irizarry, R.A., Jaffee, H.A., Wu, Z., Speed, T.P., (2004) Bioinformatics (Oxf.), 20, pp. 323-331
- Mootha, V.K., Lindgren, C.M., Eriksson, K.F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Groop, L.C., (2003) Nat. Genet, 34, pp. 267-273
- de la Mata, M., Alonso, C.R., Kadener, S., Fededa, J.P., Blaustein, M., Pelisch, F., Cramer, P., Kornblihtt, A.R., (2003) Mol. Cell, 12, pp. 525-532
- Kadener, S., Cramer, P., Nogues, G., Cazalla, D., de la Mata, M., Fededa, J.P., Werbajh, S.E., Kornblihtt, A.R., (2001) EMBO J, 20, pp. 5759-5768
- Newman, J.C., Weiner, A.M., (2005) Genome Biol, 6, pp. R81
- Dresios, J., Aschrafi, A., Owens, G.C., Vanderklish, P.W., Edelman, G.M., Mauro, V.P., (2005) Proc. Natl. Acad. Sci. U. S. A, 102, pp. 1865-1870
- Smart, F., Aschrafi, A., Atkins, A., Owens, G.C., Pilotte, J., Cunningham, B.A., Vanderklish, P.W., (2007) J. Neurochem, 101, pp. 1367-1379
- Kita, H., Carmichael, J., Swartz, J., Muro, S., Wyttenbach, A., Matsubara, K., Rubinsztein, D.C., Kato, K., (2002) Hum. Mol. Genet, 11, pp. 2279-2287
- Holbert, S., Denghien, I., Kiechle, T., Rosenblatt, A., Wellington, C., Hayden, M.R., Margolis, R.L., Neri, C., (2001) Proc. Natl. Acad. Sci. U. S. A, 98, pp. 1811-1816
- Chattopadhyay, B., Ghosh, S., Gangopadhyay, P.K., Das, S.K., Roy, T., Sinha, K.K., Jha, D.K., Bhattacharyya, N.P., (2003) Neurosci. Lett, 345, pp. 93-96
- Andresen, J.M., Gayan, J., Cherny, S.S., Brocklebank, D., Alkorta-Aranburu, G., Addis, E.A., Cardon, L.R., Wexler, N.S., (2007) J. Med. Genet, 44, pp. 44-50
- Arango, M., Holbert, S., Zala, D., Brouillet, E., Pearson, J., Regulier, E., Thakur, A.K., Neri, C., (2006) J. Neurosci, 26, pp. 4649-4659
- Kornblihtt, A.R., (2005) Curr. Opin. Cell Biol, 17, pp. 262-268
- Furger, A., O'Sullivan, J.M., Binnie, A., Lee, B.A., Proudfoot, N.J., (2002) Genes Dev, 16, pp. 2792-2799
- Fong, Y.W., Zhou, Q., (2001) Nature, 414, pp. 929-933
- Neubauer, G., King, A., Rappsilber, J., Calvio, C., Watson, M., Ajuh, P., Sleeman, J., Mann, M., (1998) Nat. Genet, 20, pp. 46-50
- Stalteri, M.A., Harrison, A.P., (2007) BMC Bioinformatics, 8, p. 13
Citas:
---------- APA ----------
Pearson, J.L., Robinson, T.J., Muñoz, M.J., Kornblihtt, A.R. & Garcia-Blanco, M.A.
(2008)
. Identification of the cellular targets of the transcription factor TCERG1 reveals a prevalent role in mrna processing. Journal of Biological Chemistry, 283(12), 7949-7961.
http://dx.doi.org/10.1074/jbc.M709402200---------- CHICAGO ----------
Pearson, J.L., Robinson, T.J., Muñoz, M.J., Kornblihtt, A.R., Garcia-Blanco, M.A.
"Identification of the cellular targets of the transcription factor TCERG1 reveals a prevalent role in mrna processing"
. Journal of Biological Chemistry 283, no. 12
(2008) : 7949-7961.
http://dx.doi.org/10.1074/jbc.M709402200---------- MLA ----------
Pearson, J.L., Robinson, T.J., Muñoz, M.J., Kornblihtt, A.R., Garcia-Blanco, M.A.
"Identification of the cellular targets of the transcription factor TCERG1 reveals a prevalent role in mrna processing"
. Journal of Biological Chemistry, vol. 283, no. 12, 2008, pp. 7949-7961.
http://dx.doi.org/10.1074/jbc.M709402200---------- VANCOUVER ----------
Pearson, J.L., Robinson, T.J., Muñoz, M.J., Kornblihtt, A.R., Garcia-Blanco, M.A. Identification of the cellular targets of the transcription factor TCERG1 reveals a prevalent role in mrna processing. J. Biol. Chem. 2008;283(12):7949-7961.
http://dx.doi.org/10.1074/jbc.M709402200