A genome-wide in situhybridization map of RNA-binding proteins reveals anatomically restricted expression in the developing mouse brain

BMC Developmental Biology - Tập 5 Số 1 - 2005
Adrienne E. McKee1, Emmanuel Minet2, Charlene A. Stern2, Shervin Riahi2, Charles D. Stiles2, Pamela A. Silver2
1Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
2Department of Cancer Biology, The Dana-Farber Cancer Institute, Boston, MA, 02115, USA

Tóm tắt

AbstractBackgroundIn eukaryotic cells, RNA-binding proteins (RBPs) contribute to gene expression by regulating the form, abundance, and stability of both coding and non-coding RNA. In the vertebrate brain, RBPs account for many distinctive features of RNA processing such as activity-dependent transcript localization and localized protein synthesis. Several RBPs with activities that are important for the proper function of adult brain have been identified, but how many RBPs exist and where these genes are expressed in the developing brain is uncharacterized.ResultsHere we describe a comprehensive catalogue of the unique RBPs encoded in the mouse genome and provide an online database of RBP expression in developing brain. We identified 380 putative RBPs in the mouse genome. Usingin situhybridization, we visualized the expression of 323 of these RBP genes in the brains of developing mice at embryonic day 13.5, when critical fate choice decisions are made and at P0, when major structural components of the adult brain are apparent. We demonstrate i) that 16 of the 323 RBPs examined show neural-specific expression at the stages we examined, and ii) that a far larger subset (221) shows regionally restricted expression in the brain. Of the regionally restricted RBPs, we describe one group that is preferentially expressed in the E13.5 ventricular areas and a second group that shows spatially restricted expression in post-mitotic regions of the embryonic brain. Additionally, we find a subset of RBPs that share the same complex pattern of expression, in proliferating regions of the embryonic and postnatal NS and peripheral tissues.ConclusionOur data show that, in contrast to their proposed ubiquitous involvement in gene regulation, most RBPs are not uniformly expressed. Here we demonstrate the region-specific expression of RBPs in proliferating vs. post-mitotic brain regions as well as cell-type-specific RBP expression. We identify uncharacterized RBPs that exhibit neural-specific expression as well as novel RBPs that show expression in non-neural tissues. The data presented here and in an online database provide a visual filter for the functional analysis of individual RBPs.

Từ khóa


Tài liệu tham khảo

Ross SE, Greenberg ME, Stiles CD: Basic helix-loop-helix factors in cortical development. Neuron. 2003, 39: 13-25. 10.1016/S0896-6273(03)00365-9.

Wilson SW, Houart C: Early steps in the development of the forebrain. Dev Cell. 2004, 6: 167-181. 10.1016/S1534-5807(04)00027-9.

Bally-Cuif L, Hammerschmidt M: Induction and patterning of neuronal development, and its connection to cell cycle control. Curr Opin Neurobiol. 2003, 13: 16-25. 10.1016/S0959-4388(03)00015-1.

Dreyfuss G, Kim VN, Kataoka N: Messenger-RNA-binding proteins and the messages they carry. Nat Rev Mol Cell Biol. 2002, 3: 195-205. 10.1038/nrm760.

Lasko P: Gene regulation at the RNA layer: RNA binding proteins in intercellular signaling networks. Sci STKE. 2003, 2003: RE6-

Orphanides G, Reinberg D: A unified theory of gene expression. Cell. 2002, 108: 439-451. 10.1016/S0092-8674(02)00655-4.

Cullen BR: Transcription and processing of human microRNA precursors. Mol Cell. 2004, 16: 861-865. 10.1016/j.molcel.2004.12.002.

Huang YS, Carson JH, Barbarese E, Richter JD: Facilitation of dendritic mRNA transport by CPEB. Genes Dev. 2003, 17: 638-653. 10.1101/gad.1053003.

Antar LN, Bassell GJ: Sunrise at the synapse: the FMRP mRNP shaping the synaptic interface. Neuron. 2003, 37: 555-558. 10.1016/S0896-6273(03)00090-4.

Tang SJ, Meulemans D, Vazquez L, Colaco N, Schuman E: A role for a rat homolog of staufen in the transport of RNA to neuronal dendrites. Neuron. 2001, 32: 463-475. 10.1016/S0896-6273(01)00493-7.

Martin KC: Local protein synthesis during axon guidance and synaptic plasticity. Curr Opin Neurobiol. 2004, 14: 305-310. 10.1016/j.conb.2004.05.009.

Huang YS, Richter JD: Regulation of local mRNA translation. Curr Opin Cell Biol. 2004, 16: 308-313. 10.1016/j.ceb.2004.03.002.

Agnes F, Perron M: RNA-binding proteins and neural development: a matter of targets and complexes. Neuroreport. 2004, 15: 2567-2570. 10.1097/00001756-200412030-00001.

Perrone-Bizzozero N, Bolognani F: Role of HuD and other RNA-binding proteins in neural development and plasticity. J Neurosci Res. 2002, 68: 121-126. 10.1002/jnr.10175.

Ule J, Jensen KB, Ruggiu M, Mele A, Ule A, Darnell RB: CLIP identifies Nova-regulated RNA networks in the brain. Science. 2003, 302: 1212-1215. 10.1126/science.1090095.

Jensen KB, Dredge BK, Stefani G, Zhong R, Buckanovich RJ, Okano HJ, Yang YY, Darnell RB: Nova-1 regulates neuron-specific alternative splicing and is essential for neuronal viability. Neuron. 2000, 25: 359-371. 10.1016/S0896-6273(00)80900-9.

Larocque D, Galarneau A, Liu HN, Scott M, Almazan G, Richard S: Protection of p27(Kip1) mRNA by quaking RNA binding proteins promotes oligodendrocyte differentiation. Nat Neurosci. 2005, 8: 27-33. 10.1038/nn1359.

Sakakibara S, Nakamura Y, Yoshida T, Shibata S, Koike M, Takano H, Ueda S, Uchiyama Y, Noda T, Okano H: RNA-binding protein Musashi family: roles for CNS stem cells and a subpopulation of ependymal cells revealed by targeted disruption and antisense ablation. Proc Natl Acad Sci U S A. 2002, 99: 15194-15199. 10.1073/pnas.232087499.

Pascale A, Gusev PA, Amadio M, Dottorini T, Govoni S, Alkon DL, Quattrone A: Increase of the RNA-binding protein HuD and posttranscriptional up-regulation of the GAP-43 gene during spatial memory. Proc Natl Acad Sci U S A. 2004, 101: 1217-1222. 10.1073/pnas.0307674100.

Jin P, Alisch RS, Warren ST: RNA and microRNAs in fragile X mental retardation. Nat Cell Biol. 2004, 6: 1048-1053. 10.1038/ncb1104-1048.

Dubnau J, Chiang AS, Grady L, Barditch J, Gossweiler S, McNeil J, Smith P, Buldoc F, Scott R, Certa U, Broger C, Tully T: The staufen/pumilio pathway is involved in Drosophila long-term memory. Curr Biol. 2003, 13: 286-296. 10.1016/S0960-9822(03)00064-2.

Miller S, Yasuda M, Coats JK, Jones Y, Martone ME, Mayford M: Disruption of dendritic translation of CaMKIIalpha impairs stabilization of synaptic plasticity and memory consolidation. Neuron. 2002, 36: 507-519. 10.1016/S0896-6273(02)00978-9.

Kang H, Schuman EM: A requirement for local protein synthesis in neurotrophin-induced hippocampal synaptic plasticity. Science. 1996, 273: 1402-1406.

Reymond A, Marigo V, Yaylaoglu MB, Leoni A, Ucla C, Scamuffa N, Caccioppoli C, Dermitzakis ET, Lyle R, Banfi S, Eichele G, Antonarakis SE, Ballabio A: Human chromosome 21 gene expression atlas in the mouse. Nature. 2002, 420: 582-586. 10.1038/nature01178.

Gray PA, Fu H, Luo P, Zhao Q, Yu J, Ferrari A, Tenzen T, Yuk DI, Tsung EF, Cai Z, Alberta JA, Cheng LP, Liu Y, Stenman JM, Valerius MT, Billings N, Kim HA, Greenberg ME, McMahon AP, Rowitch DH, Stiles CD, Ma Q: Mouse brain organization revealed through direct genome-scale TF expression analysis. Science. 2004, 306: 2255-2257. 10.1126/science.1104935.

Gitton Y, Dahmane N, Baik S, Ruiz i Altaba A, Neidhardt L, Scholze M, Herrmann BG, Kahlem P, Benkahla A, Schrinner S, Yildirimman R, Herwig R, Lehrach H, Yaspo ML: A gene expression map of human chromosome 21 orthologues in the mouse. Nature. 2002, 420: 586-590. 10.1038/nature01270.

Saunders LR, Barber GN: The dsRNA binding protein family: critical roles, diverse cellular functions. Faseb J. 2003, 17: 961-983. 10.1096/fj.02-0958rev.

Nagai K: RNA-protein complexes. Curr Opin Struct Biol. 1996, 6: 53-61. 10.1016/S0959-440X(96)80095-9.

Burd CG, Dreyfuss G: Conserved structures and diversity of functions of RNA-binding proteins. Science. 1994, 265: 615-621.

Wheeler DL, Church DM, Edgar R, Federhen S, Helmberg W, Madden TL, Pontius JU, Schuler GD, Schriml LM, Sequeira E, Suzek TO, Tatusova TA, Wagner L: Database resources of the National Center for Biotechnology Information: update. Nucleic Acids Res. 2004, 32: D35-40. 10.1093/nar/gkh073.

Sonnhammer EL, Eddy SR, Birney E, Bateman A, Durbin R: Pfam: multiple sequence alignments and HMM-profiles of protein domains. Nucleic Acids Res. 1998, 26: 320-322. 10.1093/nar/26.1.320.

Thomas PD, Campbell MJ, Kejariwal A, Mi H, Karlak B, Daverman R, Diemer K, Muruganujan A, Narechania A: PANTHER: a library of protein families and subfamilies indexed by function. Genome Res. 2003, 13: 2129-2141. 10.1101/gr.772403.

http://mahoney.chip.org/mahoney/RBP.

Buckanovich RJ, Posner JB, Darnell RB: Nova, the paraneoplastic Ri antigen, is homologous to an RNA-binding protein and is specifically expressed in the developing motor system. Neuron. 1993, 11: 657-672. 10.1016/0896-6273(93)90077-5.

Okano HJ, Darnell RB: A hierarchy of Hu RNA binding proteins in developing and adult neurons. J Neurosci. 1997, 17: 3024-3037.

Kiehl TR, Shibata H, Vo T, Huynh DP, Pulst SM: Identification and expression of a mouse ortholog of A2BP1. Mamm Genome. 2001, 12: 595-601. 10.1007/s00335-001-2056-4.

Sakakibara S, Okano H: Expression of neural RNA-binding proteins in the postnatal CNS: implications of their roles in neuronal and glial cell development. J Neurosci. 1997, 17: 8300-8312.

Sakakibara S, Nakamura Y, Satoh H, Okano H: Rna-binding protein Musashi2: developmentally regulated expression in neural precursor cells and subpopulations of neurons in mammalian CNS. J Neurosci. 2001, 21: 8091-8107.

Blackshaw S, Harpavat S, Trimarchi J, Cai L, Huang H, Kuo WP, Weber G, Lee K, Fraioli RE, Cho SH, Yung R, Asch E, Ohno-Machado L, Wong WH, Cepko CL: Genomic analysis of mouse retinal development. PLoS Biol. 2004, 2: E247-10.1371/journal.pbio.0020247.

Lillevali K, Kulla A, Ord T: Comparative expression analysis of the genes encoding polypyrimidine tract binding protein (PTB) and its neural homologue (brPTB) in prenatal and postnatal mouse brain. Mech Dev. 2001, 101: 217-220. 10.1016/S0925-4773(00)00566-9.

Zhang W, Liu H, Han K, Grabowski PJ: Region-specific alternative splicing in the nervous system: implications for regulation by the RNA-binding protein NAPOR. Rna. 2002, 8: 671-685. 10.1017/S1355838202027036.

Grabowski PJ, Black DL: Alternative RNA splicing in the nervous system. Prog Neurobiol. 2001, 65: 289-308. 10.1016/S0301-0082(01)00007-7.

Niehrs C, Pollet N: Synexpression groups in eukaryotes. Nature. 1999, 402: 483-487. 10.1038/990025.

Patton JG, Porro EB, Galceran J, Tempst P, Nadal-Ginard B: Cloning and characterization of PSF, a novel pre-mRNA splicing factor. Genes Dev. 1993, 7: 393-406.

Hahm B, Cho OH, Kim JE, Kim YK, Kim JH, Oh YL, Jang SK: Polypyrimidine tract-binding protein interacts with HnRNP L. FEBS Lett. 1998, 425: 401-406. 10.1016/S0014-5793(98)00269-5.

Eperon IC, Makarova OV, Mayeda A, Munroe SH, Caceres JF, Hayward DG, Krainer AR: Selection of alternative 5' splice sites: role of U1 snRNP and models for the antagonistic effects of SF2/ASF and hnRNP A1. Mol Cell Biol. 2000, 20: 8303-8318. 10.1128/MCB.20.22.8303-8318.2000.

Hieronymus H, Silver PA: A systems view of mRNP biology. Genes Dev. 2004, 18: 2845-2860. 10.1101/gad.1256904.

Mody M, Cao Y, Cui Z, Tay KY, Shyong A, Shimizu E, Pham K, Schultz P, Welsh D, Tsien JZ: Genome-wide gene expression profiles of the developing mouse hippocampus. Proc Natl Acad Sci U S A. 2001, 98: 8862-8867. 10.1073/pnas.141244998.

Mills JC, Andersson N, Hong CV, Stappenbeck TS, Gordon JI: Molecular characterization of mouse gastric epithelial progenitor cells. Proc Natl Acad Sci U S A. 2002, 99: 14819-14824. 10.1073/pnas.192574799.

Stappenbeck TS, Hooper LV, Gordon JI: Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc Natl Acad Sci U S A. 2002, 99: 15451-15455. 10.1073/pnas.202604299.

Harris MN, Ozpolat B, Abdi F, Gu S, Legler A, Mawuenyega KG, Tirado-Gomez M, Lopez-Berestein G, Chen X: Comparative proteomic analysis of all-trans-retinoic acid treatment reveals systematic posttranscriptional control mechanisms in acute promyelocytic leukemia. Blood. 2004, 104: 1314-1323. 10.1182/blood-2004-01-0046.

Thông tin
Thông tin xuất bản

BMC Developmental Biology

Tập 5 Số 1

Thông tin tác giả