- Open Access
Matrin 3 is a co-factor for HIV-1 Rev in regulating post-transcriptional viral gene expression
© Yedavalli and Jeang; licensee BioMed Central Ltd. 2011
- Received: 16 February 2011
- Accepted: 20 July 2011
- Published: 20 July 2011
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.
- Matrin 3
- RNA export
- nuclear matrix protein
The nucleus is a highly organized structure. Chromosomes occupy discrete regions, and specific proteins and nucleic acids are enriched in subnuclear structures such as nuclear lamina, nucleoli, Cajal bodies, nuclear speckles, and paraspeckles [1–6]. The nuclear matrix, a network of underlying filaments in the cell nucleus, shapes the nuclear architecture and functions in genome maintenance, transcription and RNA metabolism [7–17]. Accordingly, the nuclear matrix has important roles in tissue development and cellular proliferation; and the disruption of nuclear organization is often correlated with disease states such as the loss of subnuclear promyelocytic leukemia bodies in acute promyelocytic leukemia [18–21].
HIV-1 gene expression and replication are regulated at transcriptional and post-transcriptional steps including the transactivation of the HIV-1 LTR by Tat  and the export of unspliced or partially spliced viral RNAs from the nucleus to the cytoplasm by Rev [23–26]. Rev is a trans-acting viral protein which binds to a cis-acting Rev responsive element (RRE) present in unspliced and partially spliced HIV transcripts. Rev has been shown to interact with cellular proteins CRM1, DDX3, PIMT and others to mediate the export of unspliced and singly spliced viral RNAs [27–30]. The mechanism of viral RNA export by Rev is discrete from the export pathways used by fully spliced HIV-1 mRNAs, CTE- (constitutive transport element) dependent RNAs, and cellular mRNAs [31–43].
Recently, numerous studies have implicated the nuclear matrix in gene transcription, RNA splicing, and transport of cellular RNAs [5, 7, 9, 44, 45]; however, the role of the nuclear matrix in HIV-1 gene expression has been poorly explored [46–48]. Here, we identify Matrin 3 as a key component of factors that mediate the post-transcriptional regulation of HIV-1. Matrin 3 is a highly conserved inner nuclear matrix protein which has been previously shown to play a role in transcription [49–52]. It interacts with other nuclear matrix proteins to form the internal fibrogranular network; it acts in the nuclear retention of promiscuously A-to-I edited RNAs in cooperation with p54(nrb) and PSF [53, 54]; it participates in NMDA-induced neuronal death; it modulates the promoter activity of genes proximal to matrix/scaffold attachment region (MAR/SAR) ; and it is involved in the repair of double strand breaks . Our current findings implicate that Matrin 3 also influences the post-transcriptional expression of a subset of HIV-1 mRNAs.
Matrin 3 enhances Rev/RRE directed gene expression
List of Human and Mouse PTB-1 interacting proteins identified by yeast 2 hybrid assay.
PTB-1 interacting proteins identified by yeast 2 hybrid assay
A) Interacting with Human PTB-1
Calcium and integrin binding 1
CIB1; CIB; kinase-interacting protein 1; KIP1
Cleavage stimulation factor, 3' pre-RNA, subunit 2, 64 kD, tau
Homeodomain-interacting protein kinase 1 isoform1
poly(rC) binding protein 1
RNA binding motif protein 10
heterogeneous nuclear ribonucleoprotein K, isoform b
heterogeneous nuclear ribonucleoprotein L
A) Interacting with Mouse PTB-1
arylhydrocarbon receptor nuclear translocator
ARNT, hypoxia-inducible factor 1, beta subunit; dioxin receptor
Calcium and integrin binding 1
CIB1; CIB; KINASE-INTERACTING PROTEIN 1; KIP1
DAZ associated protein 2
nuclear receptor coactivator 6
RNA binding motif protein 10
protein BAT2-like 1
hexaribonucleotide binding protein 3
HRNBP3; RBFOX3; FOX3
G protein pathway suppressor 2
proline rich 3
tripartite motif-containing 8
zinc finger, CCHC domain containing 2
zinc finger protein 36, C3H type, homolog
ZFP36A, tristetraprolin; NUP475
neuro-oncological ventral antigen 1
neuro-oncological ventral antigen 2
We next investigated if Matrin 3 acts at steps post transcription. Rev is required for the cytoplasmic localization of unspliced and partially spliced HIV-1 mRNAs that encode for viral Gag, Env, Vif and Vpu proteins. Rev binds to an RRE-RNA motif in these RNAs [60, 61]. Unlike fully spliced viral RNAs, these transcripts contain cis-inhibitory RNA elements which restrict their export from the nucleus into the cytoplasm in the absence of Rev binding to the RRE motif. The binding of Rev to the RRE frees this restriction, and Gag protein expression is thus increased by several fold compared to its expression in the absence of Rev [60, 61].
We checked if Matrin 3 affects Rev-mediated post-transcriptional processes by using a CMV-promoter driven Gag-Pol-RRE expression plasmid as a reporter. HeLa cells were transfected with wild type and mutant Matrin 3 together with pCMV Gag-Pol RRE, as indicated; and 24 hours later, cells were harvested and cell lysates were analyzed by Western blotting. Figure 1B (lanes 1 and 2) shows that Matrin 3 did not alter the expression of Gag in the absence of Rev; however, in the presence of Rev, Matrin 3 increased Gag expression by approximately 10 fold (Figure 1B, lanes 3 and 4). These results support a role for Matrin 3 in Rev-dependent expression of RRE-containing HIV-1 transcripts.
The CTE is a cis-motif found in RNAs from simple type D retroviruses . It recruits cellular RNA-binding proteins that act to export unspliced or partially spliced viral mRNAs from the nucleus into the cytoplasm [39, 41]. Artificial placement of the CTE into HIV-1 Gag RNA facilitates its cytoplasmic export and expression, independent of Rev/RRE function . Indeed, CTE and Rev/RRE describe two separate pathways such that the inhibition of either pathway does not affect the export of RNA through the other pathway [34, 35]. We next assayed a Gag expression vector in which the RRE was replaced with a CTE. Unlike the results from Gal-Pol-RRE (Figure 1b), we found that the over expression of Matrin 3 had no effect on Gag-Pol-CTE expression (Figure 1C, lanes 5 and 6).
Matrin 3 interacts with Rev
Matrin 3 RNA recognition motifs (RRM) 3 are required for activity on Rev/RRE
Matrin 3 increases the stability and nuclear export of HIV-1 RRE-containing transcripts
We next investigated the consequence of increased Matrin 3 expression on cytoplasmic distribution of unspliced versus spliced viral RNAs. We co-transfected HeLa cells with pNL4-3 and Matrin 3, and fractionated cellular RNAs into total, cytoplasmic, or nuclear constituents. We isolated the RNAs from these fractions and analyzed them by qRT-PCR for the levels of unspliced and spliced RNAs using primers specific for the 9 kb or the 1.8 kb viral RNA. We used GAPDH as a normalization control for our fractionation (GAPDH; Figure 5B). Consistent with the Northern blot results, there was a 3 fold increase in expression of unspliced viral RNA in the cells (total 9 kb; Figure 5B), but interestingly the amount of 9 kb viral RNA distributed into the cytoplasm of pCMV-HA-Matrin 3 expressing cells was 10 fold higher than that found in pCMV-HA expressing cells (cytoplasmic 9 kb; Figure 5B; also see Additional file 3, Figure S3). By contrast, the distribution and expression of spliced RNA remained unchanged in the presence of increased Matrin 3 expression (1.8 kb; Figure 5B). These results are consistent with the interpretation that Matrin 3 can selectively stabilize and increase the nuclear to cytoplasmic distribution of unspliced 9 kb vs. spliced 1.8 kb HIV-1 RNAs.
Here, we have shown that nuclear matrix protein Matrin 3 influences the expression of HIV-1 RRE-containing mRNAs. Matrin 3 acts post-transcriptionally via Rev/RRE to increase the expression of HIV-1 Rev/RRE dependent unspliced or partially spliced transcripts. This activity requires Matrin 3 to bind Rev-dependent RRE-containing RNA and appears to lead to the stabilization and nuclear to cytoplasmic export of RRE-containing HIV-1 transcripts.
Previously it was shown that Matrin 3 exists in cells complexed with PSF (PTBP associated splicing factor) and nrbp54 [53, 65–67]. Others have found that PSF binds to instability elements (INS) contained within the HIV-1 transcripts and suppresses the expression of these RNAs . The INS elements are primarily present in the RRE-containing unspliced and partially spliced viral transcripts [31, 64, 68–72]. It is possible that some of the effects that we have observed from Matrin 3 may be due to its interaction with PSF and p54nrb. That Matrin 3 might counter the reported PSF-suppression of RNA expression has not been explored here, but it remains important to establish and clarify this mechanistic interaction in the future.
Our results are compatible with a model in which Matrin 3 binds to RRE containing transcripts and stabilizes them in the presence of Rev, which then directs these viral transcripts for export out of the nucleus. This interpretation is supported by our observation that Rev - Matrin 3 interaction is RRE-RNA dependent, and Matrin 3 activity requires the presence of Rev and RRE-containing RNA. Further experiments are needed to answer the mechanistic details of how Matrin 3 and Rev cooperate in their interactions with RRE-containing RNA. One intriguing finding is that Matrin 3 has been identified as a constituent of the nuclear pore proteomes ; this localization would be compatible with Matrin 3 being a part of an RNP-complex that exits the nucleus into the cytoplasm through the nuclear pore. Also of interest, Bushman et al.  recently performed a meta-analysis of published genome-wide siRNA screening of cellular factors important for HIV-1 replication. They used a graph theory clustering algorithm (MCODE) to assemble a HIV-1 host interactome in which nuclear matrix structure (Matrin 3) was identified as an interactor with the molecular chaperone cluster identified by siRNA-screening as involved in the assembly of viral proteins. Our evidence here for a role of Matrin 3 in HIV-1 post-transcriptional RNA expression is consistent with the above analysis. In conclusion, the implication of Matrin 3 as an additional Rev co-factor adds further complexity to the understanding of post-transcriptional regulation of unspliced/partially spliced HIV-1 RNA. Although it remains to be established, Matrin 3 may be a cellular factor that counters the nuclear retention through INS elements of HIV-1 unspliced/partially spliced RNAs.
Full-length Matrin 3 clone was purchased from Open Biosystems and cloned into pCMV-HA vector (Clontech) by PCR. HIV-1 LTR luciferase plasmid, pCMV-NL-GagPol-RRE and pCMV-NL-GagPol-CTE were from E. Freed and D. Rekosh. Plasmids p37 and p37RRE were kindly provided by B. Felber  and cloned into pcDNA3.
Cell Culture, Transfection, and Reporter Assays
Cell propagation, transfection, qRT-PCR and reporter assays were as described previously [28, 29]. All transfections were repeated three or more times and were normalized to β-galactosidase activity expressed from a co-transfected pCMV-β (Clontech).
Mouse monoclonal anti-HA (Sigma Chemical); mouse monoclonal Matrin 3, (Abcam) and rabbit anti-GFP and anti-HA (Cell Sciences) are commercially available.
Western Blotting, and Immunoprecipitation
Western blotting and immunoprecipitation were performed as described previously [28, 29]. Briefly, the cells were washed twice with PBS and lysed with sample buffer [100 mMTris (pH6.8), 4%SDS, 20% glycerol, 5% β-mercaptoethanol, and 0.05% bromophenol blue]. Cell lysates were boiled for 10 minutes, and loaded onto a SDS/PAGE gel and electrophoresed. The gel was electroblotted onto Immobilon-P membranes (Millipore) and probed with the primary antibodies, followed by incubation with anti-rabbit, anti-mouse, or anti-human alkaline phosphatase-conjugated secondary antibody and detected using a chemiluminescence substrate (Applied Biosystems).
RNA isolation, Northern blotting and qRT-PCR
Total RNA from cells was extracted with Tri-Reagent (Sigma-Aldrich). Nuclear and cytoplasmic RNAs were isolated by cell fractionation (Paris Kit; Applied Biosystems), and RNA was isolated with Tri-Reagent. Northern blots were performed as described previously . Extracted RNA was analyzed by qRT-PCR using the iScript One-Step RT-PCR Kit with SYBR Green (Bio-Rad) according to manufacturer's instructions. Samples were reverse-transcribed at 50°C for 30 minutes, and amplification was performed after an initial step at 95°C for 10 minutes, followed by 20-40 cycles at 95°C for 30 s, 55°C for 30 s, and 72°C for 60 s. The primers and their sequences used in the analyses have been previously described . Primers for unspliced transcripts were Primer A 5′-GTCTCTCTGGTTAGACCAG-3′, Primer C 5′-CTAGTCAAAATTTTTGGCGTACTC-3′ and primer A and sj4.7A 5′- TTGGGAGGTGGGTTGCTTTGATAGAG-3 for spliced 2 Kb transcript. For GAPDH forward 5′ CTCTGCTCCTCCTGTTCGAC 3′ and GAPDH reverse 5′ TTAAAAGCAGCCCTGGTGAC 3′ primers were used.
Co-immunoprecipitation assay has been described previously [28, 29]. Cell lysates were prepared in RIPA buffer [Tris-buffered saline (pH 8.0) containing 1% Triton X-100 or Nonidet P-40, 1 mg of BSA/mL, and 1 mM EDTA] containing (phenylmethylsulfonyl fluoride and aprotinin 10 μg/mL), 0.5% sodium deoxycholate, and 0.1% SDS. Cell lysates were prepared and incubated at 4°C overnight with the indicated antibodies and immune complexes were pulled down using protein G-agarose beads and analyzed by Western blotting.
Work in KTJ's laboratory was supported in part by Intramural funds from NIAID, and by the Intramural AIDS Targeted Antiviral Program (IATAP) from the office of the Director, NIH. We thank members of KTJ's laboratory for reading and commenting on the manuscript, and Barbara Felber for sharing several critical reagents. We are grateful to Anna Kula and Alessandro Marcello for sharing data in their paper prior to publication .
- Vlcek S, Dechat T, Foisner R: Nuclear envelope and nuclear matrix: interactions and dynamics. Cell Mol Life Sci. 2001, 58: 1758-1765. 10.1007/PL00000815.View ArticlePubMedGoogle Scholar
- Baxter J, Merkenschlager M, Fisher AG: Nuclear organisation and gene expression. Curr Opin Cell Biol. 2002, 14: 372-376. 10.1016/S0955-0674(02)00339-3.View ArticlePubMedGoogle Scholar
- 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. 10.1023/A:1024943214431.View ArticlePubMedGoogle Scholar
- Stein GS: Gene expression in nuclear microenvironments for biological control and cancer. Cancer Biol Ther. 2007, 6: 1817-1821. 10.4161/cbt.6.11.5294.View ArticlePubMedGoogle Scholar
- Stein GS, Davie JR, Knowlton JR, Zaidi SK: Nuclear microenvironments and cancer. J Cell Biochem. 2008, 104: 1949-1952. 10.1002/jcb.21846.View ArticlePubMedGoogle Scholar
- Fedorova E, Zink D: Nuclear architecture and gene regulation. Biochim Biophys Acta. 2008, 1783: 2174-2184. 10.1016/j.bbamcr.2008.07.018.View ArticlePubMedGoogle Scholar
- Berezney R, Coffey DS: Nuclear protein matrix: association with newly synthesized DNA. Science. 1975, 189: 291-293. 10.1126/science.1145202.View ArticlePubMedGoogle Scholar
- Cook PR: The nucleoskeleton: artefact, passive framework or active site?. J Cell Sci. 1988, 90 (Pt 1): 1-6.PubMedGoogle Scholar
- Nickerson JA: Nuclear dreams: the malignant alteration of nuclear architecture. J Cell Biochem. 1998, 70: 172-180. 10.1002/(SICI)1097-4644(19980801)70:2<172::AID-JCB3>3.0.CO;2-L.View ArticlePubMedGoogle Scholar
- 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.View ArticlePubMedGoogle Scholar
- Berezney R: Regulating the mammalian genome: the role of nuclear architecture. Adv Enzyme Regul. 2002, 42: 39-52.View ArticlePubMedGoogle Scholar
- 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. 10.1016/j.tcb.2003.09.009.View ArticlePubMedGoogle Scholar
- 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. 10.1038/sj.embor.7400337.PubMed CentralView ArticlePubMedGoogle Scholar
- Misteli T: Beyond the sequence: cellular organization of genome function. Cell. 2007, 128: 787-800. 10.1016/j.cell.2007.01.028.View ArticlePubMedGoogle Scholar
- 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. 10.1038/nrg2041.View ArticlePubMedGoogle Scholar
- 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. 10.1002/jcb.21834.PubMed CentralView ArticlePubMedGoogle Scholar
- Cohen TV, Hernandez L, Stewart CL: Functions of the nuclear envelope and lamina in development and disease. Biochem Soc Trans. 2008, 36: 1329-1334. 10.1042/BST0361329.View ArticlePubMedGoogle Scholar
- 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. 10.1146/annurev.bb.15.060186.002325.View ArticlePubMedGoogle Scholar
- Pederson T: Half a century of "the nuclear matrix". Mol Biol Cell. 2000, 11: 799-805.PubMed CentralView ArticlePubMedGoogle Scholar
- 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.PubMedGoogle Scholar
- Sjakste N, Sjakste T, Vikmanis U: Role of the nuclear matrix proteins in malignant transformation and cancer diagnosis. Exp Oncol. 2004, 26: 170-178.PubMedGoogle Scholar
- Berkhout B, Silverman RH, Jeang KT: Tat trans-activates the human immunodeficiency virus through a nascent RNA target. Cell. 1989, 59: 273-282. 10.1016/0092-8674(89)90289-4.View ArticlePubMedGoogle Scholar
- 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. 10.1038/338254a0.View ArticlePubMedGoogle Scholar
- Zapp ML, Green MR: Sequence-specific RNA binding by the HIV-1 Rev protein. Nature. 1989, 342: 714-716. 10.1038/342714a0.View ArticlePubMedGoogle Scholar
- 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.PubMed CentralPubMedGoogle Scholar
- 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. 10.2217/17460918.104.22.1687.View ArticlePubMedGoogle Scholar
- Cochrane A: Inhibition of HIV-1 gene expression by Sam68 Delta C: multiple targets but a common mechanism?. Retrovirology. 2009, 6: 22-10.1186/1742-4690-6-22.PubMed CentralView ArticlePubMedGoogle Scholar
- 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. 10.1016/j.cell.2004.09.029.View ArticlePubMedGoogle Scholar
- Yedavalli VS, Jeang KT: Trimethylguanosine capping selectively promotes expression of Rev-dependent HIV-1 RNAs. Proc Natl Acad Sci USA. 2010, 107: 14787-14792. 10.1073/pnas.1009490107.PubMed CentralView ArticlePubMedGoogle Scholar
- Yedavalli VS, Jeang KT: Rev-ing up post-transcriptional HIV-1 RNA expression. RNA Biol. 2011, 8: (2):195-9.PubMed CentralView ArticlePubMedGoogle Scholar
- 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. 10.1073/pnas.86.5.1495.PubMed CentralView ArticlePubMedGoogle Scholar
- 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. 10.1073/pnas.91.4.1256.PubMed CentralView ArticlePubMedGoogle Scholar
- 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. 10.1016/S0960-9822(06)00335-6.View ArticlePubMedGoogle Scholar
- 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. 10.1093/emboj/16.24.7500.PubMed CentralView ArticlePubMedGoogle Scholar
- 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. 10.1016/S0960-9822(06)00288-0.View ArticlePubMedGoogle Scholar
- Fornerod M, Ohno M, Yoshida M, Mattaj IW: CRM1 is an export receptor for leucine-rich nuclear export signals. Cell. 1997, 90: 1051-1060. 10.1016/S0092-8674(00)80371-2.View ArticlePubMedGoogle Scholar
- 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. 10.1038/36894.View ArticlePubMedGoogle Scholar
- 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. 10.1074/jbc.273.50.33414.View ArticlePubMedGoogle Scholar
- 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.PubMed CentralView ArticlePubMedGoogle Scholar
- 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. 10.1083/jcb.150.4.695.PubMed CentralView ArticlePubMedGoogle Scholar
- 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. 10.1017/S1355838200000078.PubMed CentralView ArticlePubMedGoogle Scholar
- Clouse KN, Luo MJ, Zhou Z, Reed R: A Ran-independent pathway for export of spliced mRNA. Nat Cell Biol. 2001, 3: 97-99. 10.1038/35050625.View ArticlePubMedGoogle Scholar
- Bolinger C, Boris-Lawrie K: Mechanisms employed by retroviruses to exploit host factors for translational control of a complicated proteome. Retrovirology. 2009, 6: 8-PubMed CentralView ArticlePubMedGoogle Scholar
- 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.PubMedGoogle Scholar
- 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. 10.1073/pnas.94.9.4446.PubMed CentralView ArticlePubMedGoogle Scholar
- 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. 10.1093/emboj/cdg205.PubMed CentralView ArticlePubMedGoogle Scholar
- 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.View ArticlePubMedGoogle Scholar
- 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. 10.1038/emboj.2009.141.PubMed CentralView ArticlePubMedGoogle Scholar
- 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.PubMedGoogle Scholar
- Nakayasu H, Berezney R: Nuclear matrins: identification of the major nuclear matrix proteins. Proc Natl Acad Sci USA. 1991, 88: 10312-10316. 10.1073/pnas.88.22.10312.PubMed CentralView ArticlePubMedGoogle Scholar
- 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. 10.1016/j.bbrc.2006.12.191.View ArticlePubMedGoogle Scholar
- Zeitz MJ, Malyavantham KS, Seifert B, Berezney R: Matrin 3: chromosomal distribution and protein interactions. J Cell Biochem. 2009, 108: 125-133. 10.1002/jcb.22234.View ArticlePubMedGoogle Scholar
- 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. 10.1016/S0092-8674(01)00466-4.View ArticlePubMedGoogle Scholar
- DeCerbo J, Carmichael GG: Retention and repression: fates of hyperedited RNAs in the nucleus. Curr Opin Cell Biol. 2005, 17: 302-308. 10.1016/j.ceb.2005.04.008.View ArticlePubMedGoogle Scholar
- 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. 10.1111/j.1471-4159.2005.03235.x.View ArticlePubMedGoogle Scholar
- 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:Google Scholar
- 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: e68-10.1371/journal.ppat.0020068.PubMed CentralView ArticlePubMedGoogle Scholar
- 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. 10.1101/gad.7.3.393.View ArticlePubMedGoogle Scholar
- 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. 10.1128/MCB.23.18.6618-6630.2003.PubMed CentralView ArticlePubMedGoogle Scholar
- Lever AM, Jeang KT: Replication of human immunodeficiency virus type 1 from entry to exit. Int J Hematol. 2006, 84: 23-30. 10.1532/IJH97.06112.View ArticlePubMedGoogle Scholar
- Lever AM, Jeang KT: Insights into Cellular Factors That Regulate HIV-1 Replication in Human Cells. Biochemistry. 2011, 50: 920-931. 10.1021/bi101805f.PubMed CentralView ArticlePubMedGoogle Scholar
- 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.PubMed CentralPubMedGoogle Scholar
- 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.PubMed CentralPubMedGoogle Scholar
- 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.PubMed CentralPubMedGoogle Scholar
- Shav-Tal Y, Zipori D: PSF and p54(nrb)/NonO--multi-functional nuclear proteins. FEBS Lett. 2002, 531: 109-114. 10.1016/S0014-5793(02)03447-6.View ArticlePubMedGoogle Scholar
- 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. 10.1038/sj.emboj.7600187.PubMed CentralView ArticlePubMedGoogle Scholar
- 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.View ArticlePubMedGoogle Scholar
- 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.PubMed CentralPubMedGoogle Scholar
- 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.PubMed CentralPubMedGoogle Scholar
- 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.PubMed CentralPubMedGoogle Scholar
- 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.PubMed CentralPubMedGoogle Scholar
- 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.PubMed CentralView ArticlePubMedGoogle Scholar
- 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. 10.1083/jcb.200206106.PubMed CentralView ArticlePubMedGoogle Scholar
- 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): e1000437-10.1371/journal.ppat.1000437.PubMed CentralView ArticlePubMedGoogle Scholar
- 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: 60-10.1186/1742-4690-8-S1-A60.PubMed CentralView ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.