Matrin 3 is a co-factor for HIV-1 Rev in regulating post-transcriptional viral gene expression

Retrovirology

Kuan-Teh Jeang¹  Venkat SRK Yedavalli¹ 

[1] Molecular Virology Section, Laboratory of Molecular Microbiology, National Institutes of Allergy and Infectious Diseases, the National Institutes of Health, Bethesda, Maryland 20892-0460, USA

关键词: nuclear matrix protein;    RNA export;    Rev;    HIV-1;    Matrin 3;   

Others  :  1209417
DOI  :  10.1186/1742-4690-8-61

 received in 2011-02-16, accepted in 2011-07-20,  发布年份 2011

【 摘 要 】

Post-transcriptional regulation of HIV-1 gene expression is mediated by interactions between viral transcripts and viral/cellular proteins. For HIV-1, post-transcriptional nuclear control allows for the export of intron-containing RNAs which are normally retained in the nucleus. Specific signals on the viral RNAs, such as instability sequences (INS) and Rev responsive element (RRE), are binding sites for viral and cellular factors that serve to regulate RNA-export. The HIV-1 encoded viral Rev protein binds to the RRE found on unspliced and incompletely spliced viral RNAs. Binding by Rev directs the export of these RNAs from the nucleus to the cytoplasm. Previously, Rev co-factors have been found to include cellular factors such as CRM1, DDX3, PIMT and others. In this work, the nuclear matrix protein Matrin 3 is shown to bind Rev/RRE-containing viral RNA. This binding interaction stabilizes unspliced and partially spliced HIV-1 transcripts leading to increased cytoplasmic expression of these viral RNAs.

【 授权许可】

   
2011 Yedavalli and Jeang; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】

• [1]Vlcek S, Dechat T, Foisner R: Nuclear envelope and nuclear matrix: interactions and dynamics. Cell Mol Life Sci 2001, 58:1758-1765.
• [2]Baxter J, Merkenschlager M, Fisher AG: Nuclear organisation and gene expression. Curr Opin Cell Biol 2002, 14:372-376.
• [3]Stein GS, Lian JB, Montecino M, Stein JL, van Wijnen AJ, Javed A, Pratap J, Choi J, Zaidi SK, Gutierrez S, et al.: Nuclear microenvironments support physiological control of gene expression. Chromosome Res 2003, 11:527-536.
• [4]Stein GS: Gene expression in nuclear microenvironments for biological control and cancer. Cancer Biol Ther 2007, 6:1817-1821.
• [5]Stein GS, Davie JR, Knowlton JR, Zaidi SK: Nuclear microenvironments and cancer. J Cell Biochem 2008, 104:1949-1952.
• [6]Fedorova E, Zink D: Nuclear architecture and gene regulation. Biochim Biophys Acta 2008, 1783:2174-2184.
• [7]Berezney R, Coffey DS: Nuclear protein matrix: association with newly synthesized DNA. Science 1975, 189:291-293.
• [8]Cook PR: The nucleoskeleton: artefact, passive framework or active site? J Cell Sci 1988, 90(Pt 1):1-6.
• [9]Nickerson JA: Nuclear dreams: the malignant alteration of nuclear architecture. J Cell Biochem 1998, 70:172-180.
• [10]Wei X, Samarabandu J, Devdhar RS, Siegel AJ, Acharya R, Berezney R: Segregation of transcription and replication sites into higher order domains. Science 1998, 281:1502-1506.
• [11]Berezney R: Regulating the mammalian genome: the role of nuclear architecture. Adv Enzyme Regul 2002, 42:39-52.
• [12]Stein GS, Zaidi SK, Braastad CD, Montecino M, van Wijnen AJ, Choi JY, Stein JL, Lian JB, Javed A: Functional architecture of the nucleus: organizing the regulatory machinery for gene expression, replication and repair. Trends Cell Biol 2003, 13:584-592.
• [13]Zaidi SK, Young DW, Choi JY, Pratap J, Javed A, Montecino M, Stein JL, van Wijnen AJ, Lian JB, Stein GS: The dynamic organization of gene-regulatory machinery in nuclear microenvironments. EMBO Rep 2005, 6:128-133.
• [14]Misteli T: Beyond the sequence: cellular organization of genome function. Cell 2007, 128:787-800.
• [15]Lanctot C, Cheutin T, Cremer M, Cavalli G, Cremer T: Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions. Nat Rev Genet 2007, 8:104-115.
• [16]Malyavantham KS, Bhattacharya S, Barbeitos M, Mukherjee L, Xu J, Fackelmayer FO, Berezney R: Identifying functional neighborhoods within the cell nucleus: proximity analysis of early S-phase replicating chromatin domains to sites of transcription, RNA polymerase II, HP1gamma, matrin 3 and SAF-A. J Cell Biochem 2008, 105:391-403.
• [17]Cohen TV, Hernandez L, Stewart CL: Functions of the nuclear envelope and lamina in development and disease. Biochem Soc Trans 2008, 36:1329-1334.
• [18]Nelson WG, Pienta KJ, Barrack ER, Coffey DS: The role of the nuclear matrix in the organization and function of DNA. Annu Rev Biophys Biophys Chem 1986, 15:457-475.
• [19]Pederson T: Half a century of "the nuclear matrix". Mol Biol Cell 2000, 11:799-805.
• [20]Coffey DS: Nuclear matrix proteins as proteomic markers of preneoplastic and cancer lesions: commentary re: G. Brunagel et al., nuclear matrix protein alterations associated with colon cancer metastasis to the liver. Clin. Cancer Res., 8: 3039-3045, 2002. Clin Cancer Res 2002, 8:3031-3033.
• [21]Sjakste N, Sjakste T, Vikmanis U: Role of the nuclear matrix proteins in malignant transformation and cancer diagnosis. Exp Oncol 2004, 26:170-178.
• [22]Berkhout B, Silverman RH, Jeang KT: Tat trans-activates the human immunodeficiency virus through a nascent RNA target. Cell 1989, 59:273-282.
• [23]Malim MH, Hauber J, Le SY, Maizel JV, Cullen BR: The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature 1989, 338:254-257.
• [24]Zapp ML, Green MR: Sequence-specific RNA binding by the HIV-1 Rev protein. Nature 1989, 342:714-716.
• [25]Hope TJ, McDonald D, Huang XJ, Low J, Parslow TG: Mutational analysis of the human immunodeficiency virus type 1 Rev transactivator: essential residues near the amino terminus. J Virol 1990, 64:5360-5366.
• [26]Nekhai S, Jeang KT: Transcriptional and post-transcriptional regulation of HIV-1 gene expression: role of cellular factors for Tat and Rev. Future Microbiol 2006, 1:417-426.
• [27]Cochrane A: Inhibition of HIV-1 gene expression by Sam68 Delta C: multiple targets but a common mechanism? Retrovirology 2009, 6:22. BioMed Central Full Text
• [28]Yedavalli VS, Neuveut C, Chi YH, Kleiman L, Jeang KT: Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export function. Cell 2004, 119:381-392.
• [29]Yedavalli VS, Jeang KT: Trimethylguanosine capping selectively promotes expression of Rev-dependent HIV-1 RNAs. Proc Natl Acad Sci USA 2010, 107:14787-14792.
• [30]Yedavalli VS, Jeang KT: Rev-ing up post-transcriptional HIV-1 RNA expression. RNA Biol 2011, 8:(2):195-9.
• [31]Felber BK, Hadzopoulou-Cladaras M, Cladaras C, Copeland T, Pavlakis GN: rev protein of human immunodeficiency virus type 1 affects the stability and transport of the viral mRNA. Proc Natl Acad Sci USA 1989, 86:1495-1499.
• [32]Bray M, Prasad S, Dubay JW, Hunter E, Jeang KT, Rekosh D, Hammarskjold ML: A small element from the Mason-Pfizer monkey virus genome makes human immunodeficiency virus type 1 expression and replication Rev-independent. Proc Natl Acad Sci USA 1994, 91:1256-1260.
• [33]Neville M, Stutz F, Lee L, Davis LI, Rosbash M: The importin-beta family member Crm1p bridges the interaction between Rev and the nuclear pore complex during nuclear export. Curr Biol 1997, 7:767-775.
• [34]Pasquinelli AE, Ernst RK, Lund E, Grimm C, Zapp ML, Rekosh D, Hammarskjold ML, Dahlberg JE: The constitutive transport element (CTE) of Mason-Pfizer monkey virus (MPMV) accesses a cellular mRNA export pathway. EMBO J 1997, 16:7500-7510.
• [35]Saavedra C, Felber B, Izaurralde E: The simian retrovirus-1 constitutive transport element, unlike the HIV-1 RRE, uses factors required for cellular mRNA export. Curr Biol 1997, 7:619-628.
• [36]Fornerod M, Ohno M, Yoshida M, Mattaj IW: CRM1 is an export receptor for leucine-rich nuclear export signals. Cell 1997, 90:1051-1060.
• [37]Fukuda M, Asano S, Nakamura T, Adachi M, Yoshida M, Yanagida M, Nishida E: CRM1 is responsible for intracellular transport mediated by the nuclear export signal. Nature 1997, 390:308-311.
• [38]Askjaer P, Jensen TH, Nilsson J, Englmeier L, Kjems J: The specificity of the CRM1-Rev nuclear export signal interaction is mediated by RanGTP. J Biol Chem 1998, 273:33414-33422.
• [39]Bear J, Tan W, Zolotukhin AS, Tabernero C, Hudson EA, Felber BK: Identification of novel import and export signals of human TAP, the protein that binds to the constitutive transport element of the type D retrovirus mRNAs. Mol Cell Biol 1999, 19:6306-6317.
• [40]Strasser K, Bassler J, Hurt E: Binding of the Mex67p/Mtr2p heterodimer to FXFG, GLFG, and FG repeat nucleoporins is essential for nuclear mRNA export. J Cell Biol 2000, 150:695-706.
• [41]Stutz F, Bachi A, Doerks T, Braun IC, Seraphin B, Wilm M, Bork P, Izaurralde E: REF, an evolutionary conserved family of hnRNP-like proteins, interacts with TAP/Mex67p and participates in mRNA nuclear export. RNA 2000, 6:638-650.
• [42]Clouse KN, Luo MJ, Zhou Z, Reed R: A Ran-independent pathway for export of spliced mRNA. Nat Cell Biol 2001, 3:97-99.
• [43]Bolinger C, Boris-Lawrie K: Mechanisms employed by retroviruses to exploit host factors for translational control of a complicated proteome. Retrovirology 2009, 6:8.
• [44]Agutter PS, Richardson JC: Nuclear non-chromatin proteinaceous structures: their role in the organization and function of the interphase nucleus. J Cell Sci 1980, 44:395-435.
• [45]Nickerson JA, Krockmalnic G, Wan KM, Penman S: The nuclear matrix revealed by eluting chromatin from a cross-linked nucleu. Proc Natl Acad Sci USA 1997, 94:4446-4450.
• [46]Marcello A, Ferrari A, Pellegrini V, Pegoraro G, Lusic M, Beltram F, Giacca M: Recruitment of human cyclin T1 to nuclear bodies through direct interaction with the PML protein. EMBO J 2003, 22:2156-2166.
• [47]Marcello A, Lusic M, Pegoraro G, Pellegrini V, Beltram F, Giacca M: Nuclear organization and the control of HIV-1 transcription. Gene 2004, 326:1-11.
• [48]Dieudonne M, Maiuri P, Biancotto C, Knezevich A, Kula A, Lusic M, Marcello A: Transcriptional competence of the integrated HIV-1 provirus at the nuclear periphery. EMBO J 2009, 28:2231-2243.
• [49]Belgrader P, Dey R, Berezney R: Molecular cloning of matrin 3. A 125-kilodalton protein of the nuclear matrix contains an extensive acidic domain. J Biol Chem 1991, 266:9893-9899.
• [50]Nakayasu H, Berezney R: Nuclear matrins: identification of the major nuclear matrix proteins. Proc Natl Acad Sci USA 1991, 88:10312-10316.
• [51]Hisada-Ishii S, Ebihara M, Kobayashi N, Kitagawa Y: Bipartite nuclear localization signal of matrin 3 is essential for vertebrate cells. Biochem Biophys Res Commun 2007, 354:72-76.
• [52]Zeitz MJ, Malyavantham KS, Seifert B, Berezney R: Matrin 3: chromosomal distribution and protein interactions. J Cell Biochem 2009, 108:125-133.
• [53]Zhang Z, Carmichael GG: The fate of dsRNA in the nucleus: a p54(nrb)-containing complex mediates the nuclear retention of promiscuously A-to-I edited RNAs. Cell 2001, 106:465-475.
• [54]DeCerbo J, Carmichael GG: Retention and repression: fates of hyperedited RNAs in the nucleus. Curr Opin Cell Biol 2005, 17:302-308.
• [55]Giordano G, Sanchez-Perez AM, Montoliu C, Berezney R, Malyavantham K, Costa LG, Calvete JJ, Felipo V: Activation of NMDA receptors induces protein kinase A-mediated phosphorylation and degradation of matrin 3. Blocking these effects prevents NMDA-induced neuronal death. J Neurochem 2005, 94:808-818.
• [56]Salton M, Lerenthal Y, Wang SY, Chen DJ, Shiloh Y: Involvement of matrin 3 and SFPQ/NONO in the DNA damage response. Cell Cycle 2010., 9
• [57]Lassen KG, Ramyar KX, Bailey JR, Zhou Y, Siliciano RF: Nuclear retention of multiply spliced HIV-1 RNA in resting CD4+ T cells. PLoS Pathog 2006, 2:e68.
• [58]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.
• [59]Zolotukhin AS, Michalowski D, Bear J, Smulevitch SV, Traish AM, Peng R, Patton J, Shatsky IN, Felber BK: PSF acts through the human immunodeficiency virus type 1 mRNA instability elements to regulate virus expression. Mol Cell Biol 2003, 23:6618-6630.
• [60]Lever AM, Jeang KT: Replication of human immunodeficiency virus type 1 from entry to exit. Int J Hematol 2006, 84:23-30.
• [61]Lever AM, Jeang KT: Insights into Cellular Factors That Regulate HIV-1 Replication in Human Cells. Biochemistry 2011, 50:920-931.
• [62]Schwartz S, Campbell M, Nasioulas G, Harrison J, Felber BK, Pavlakis GN: Mutational inactivation of an inhibitory sequence in human immunodeficiency virus type 1 results in Rev-independent gag expression. J Virol 1992, 66:7176-7182.
• [63]Schwartz S, Felber BK, Pavlakis GN: Distinct RNA sequences in the gag region of human immunodeficiency virus type 1 decrease RNA stability and inhibit expression in the absence of Rev protein. J Virol 1992, 66:150-159.
• [64]Schneider R, Campbell M, Nasioulas G, Felber BK, Pavlakis GN: Inactivation of the human immunodeficiency virus type 1 inhibitory elements allows Rev-independent expression of Gag and Gag/protease and particle formation. J Virol 1997, 71:4892-4903.
• [65]Shav-Tal Y, Zipori D: PSF and p54(nrb)/NonO--multi-functional nuclear proteins. FEBS Lett 2002, 531:109-114.
• [66]Kameoka S, Duque P, Konarska MM: p54(nrb) associates with the 5' splice site within large transcription/splicing complexes. EMBO J 2004, 23:1782-1791.
• [67]Buxade M, Morrice N, Krebs DL, Proud CG: The PSF.p54nrb complex is a novel Mnk substrate that binds the mRNA for tumor necrosis factor alpha. J Biol Chem 2008, 283:57-65.
• [68]Schwartz S, Felber BK, Benko DM, Fenyo EM, Pavlakis GN: Cloning and functional analysis of multiply spliced mRNA species of human immunodeficiency virus type 1. J Virol 1990, 64:2519-2529.
• [69]Cochrane AW, Jones KS, Beidas S, Dillon PJ, Skalka AM, Rosen CA: Identification and characterization of intragenic sequences which repress human immunodeficiency virus structural gene expression. J Virol 1991, 65:5305-5313.
• [70]Maldarelli F, Martin MA, Strebel K: Identification of posttranscriptionally active inhibitory sequences in human immunodeficiency virus type 1 RNA: novel level of gene regulation. J Virol 1991, 65:5732-5743.
• [71]Nasioulas G, Zolotukhin AS, Tabernero C, Solomin L, Cunningham CP, Pavlakis GN, Felber BK: Elements distinct from human immunodeficiency virus type 1 splice sites are responsible for the Rev dependence of env mRNA. J Virol 1994, 68:2986-2993.
• [72]Shav-Tal Y, Cohen M, Lapter S, Dye B, Patton JG, Vandekerckhove J, Zipori D: Nuclear relocalization of the pre-mRNA splicing factor PSF during apoptosis involves hyperphosphorylation, masking of antigenic epitopes, and changes in protein interactions. Mol Biol Cell 2001, 12:2328-2340.
• [73]Cronshaw JM, Krutchinsky AN, Zhang W, Chait BT, Matunis MJ: Proteomic analysis of the mammalian nuclear pore complex. J Cell Biol 2002, 158:915-927.
• [74]Bushman FD, Malani N, Fernandes J, D'Orso I, Cagney G, Diamond TL, Zhou H, Hazuda DJ, Espeseth AS, König R, Bandyopadhyay S, Ideker T, Goff SP, Krogan NJ, Frankel AD, Young JA, Chanda SK: Host cell factors in HIV replication: meta-analysis of genome-wide studies. PLoS Pathog 2009, 5(5):e1000437.
• [75]Kula A, Guerra J, Knezevich A, Kleva D, Myers MP, Marcello A: Characterization of the HIV-1 RNA associated proteome identifies Matrin 3 as a nuclear cofactor of Rev function. Retrovirology 2011, 8:60. BioMed Central Full Text