LARP7

Summary

Gene Symbol: LARP7
Description: La ribonucleoprotein domain family member 7
Alias: ALAZS, HDCMA18P, PIP7S, la-related protein 7, P-TEFb-interaction protein for 7SK stability
Species: human
Products:     LARP7

Top Publications

  1. Biewenga P, Buist M, Moerland P, Ver Loren van Themaat E, van Kampen A, ten Kate F, et al. Gene expression in early stage cervical cancer. Gynecol Oncol. 2008;108:520-6 pubmed publisher
    ..Five genes (BANF1, LARP7, SCAMP1, CUEDC1 and PEBP1) showed differential expression between tumour samples from patients with and without ..
  2. Lu H, Li Z, Xue Y, Schulze Gahmen U, Johnson J, Krogan N, et al. AFF1 is a ubiquitous P-TEFb partner to enable Tat extraction of P-TEFb from 7SK snRNP and formation of SECs for HIV transactivation. Proc Natl Acad Sci U S A. 2014;111:E15-24 pubmed publisher
    ..Our data identify AFF1 as a ubiquitous P-TEFb partner and demonstrate that full Tat transactivation requires the complete SEC. ..
  3. Tyagi M, Pearson R, Karn J. Establishment of HIV latency in primary CD4+ cells is due to epigenetic transcriptional silencing and P-TEFb restriction. J Virol. 2010;84:6425-37 pubmed publisher
    ..Thus, a combination of restrictive chromatin structures at the HIV long terminal repeat and limiting P-TEFb levels contribute to transcriptional silencing leading to latency in primary CD4(+) T cells. ..
  4. Markert A, Grimm M, Martinez J, Wiesner J, Meyerhans A, Meyuhas O, et al. The La-related protein LARP7 is a component of the 7SK ribonucleoprotein and affects transcription of cellular and viral polymerase II genes. EMBO Rep. 2008;9:569-75 pubmed publisher
    ..Here, we show that the previously uncharacterized La-related protein 7 (LARP7) has a role in 7SK-mediated regulation of transcription...
  5. Krueger B, Jeronimo C, Roy B, Bouchard A, Barrandon C, Byers S, et al. LARP7 is a stable component of the 7SK snRNP while P-TEFb, HEXIM1 and hnRNP A1 are reversibly associated. Nucleic Acids Res. 2008;36:2219-29 pubmed publisher
    ..to two previously-uncharacterized proteins, the methyphosphate capping enzyme, MEPCE, and a La-related protein, LARP7. Glycerol gradient sedimentation analysis of lysates from cells treated with P-TEFb inhibitors, suggested that the ..
  6. Sobhian B, Laguette N, Yatim A, Nakamura M, Levy Y, Kiernan R, et al. HIV-1 Tat assembles a multifunctional transcription elongation complex and stably associates with the 7SK snRNP. Mol Cell. 2010;38:439-51 pubmed publisher
  7. Peterlin B, Brogie J, Price D. 7SK snRNA: a noncoding RNA that plays a major role in regulating eukaryotic transcription. Wiley Interdiscip Rev RNA. 2012;3:92-103 pubmed publisher
    ..While the Lupus antigen (La)-related protein 7 (LARP7) is a constitutive component, the methylphosphate capping enzyme (MePCE) associates secondarily to phosphorylate ..
  8. He N, Jahchan N, Hong E, Li Q, Bayfield M, Maraia R, et al. A La-related protein modulates 7SK snRNP integrity to suppress P-TEFb-dependent transcriptional elongation and tumorigenesis. Mol Cell. 2008;29:588-99 pubmed publisher
    ..Here, we identify PIP7S as a La-related protein stably associated with and required for 7SK snRNP integrity...
  9. Alazami A, Al Owain M, Alzahrani F, Shuaib T, Al Shamrani H, Al Falki Y, et al. Loss of function mutation in LARP7, chaperone of 7SK ncRNA, causes a syndrome of facial dysmorphism, intellectual disability, and primordial dwarfism. Hum Mutat. 2012;33:1429-34 pubmed publisher
    ..for PD involving depletion of 7SK, an abundant cellular noncoding RNA (ncRNA), due to mutation of its chaperone LARP7. We show that 7SK levels are tightly linked to LARP7 expression across cell lines, and that this chaperone is ..

More Information

Publications50

  1. Bruesch I, Meier P, Vital M, Pieper D, Selke K, Böhlen S, et al. Analysis of Cdcs1 colitogenic effects in the hematopoietic compartment reveals distinct microbiome interaction and a new subcongenic interval active in T cells. Mucosal Immunol. 2019;12:691-702 pubmed publisher
    ..Transfers excluded Larp7 and Alpk1 but highlighted Ifi44 as potential candidate genes...
  2. Bleich A, Büchler G, Beckwith J, Petell L, Affourtit J, King B, et al. Cdcs1 a major colitis susceptibility locus in mice; subcongenic analysis reveals genetic complexity. Inflamm Bowel Dis. 2010;16:765-75 pubmed publisher
    ..1, Cdcs1.2, and Cdcs1.3). Combining results of candidate gene approaches revealed Fcgr1, Cnn3, Larp7, and Alpk1 as highly attractive candidate genes with polymorphisms in coding or regulatory regions and expression ..
  3. Imbert Bouteille M, Mau Them F, Thévenon J, Guignard T, Gatinois V, Rivière J, et al. LARP7 variants and further delineation of the Alazami syndrome phenotypic spectrum among primordial dwarfisms: 2 sisters. Eur J Med Genet. 2019;62:161-166 pubmed publisher
    ..recognizable facial features and severe intellectual disability due to depletion or loss of function variants in LARP7. To date, 15 patients with AS have been reported...
  4. Bayfield M, Yang R, Maraia R. Conserved and divergent features of the structure and function of La and La-related proteins (LARPs). Biochim Biophys Acta. 2010;1799:365-78 pubmed publisher
    ..g., 7SK snRNP assembly by hLARP7/PIP7S)...
  5. Eichhorn C, Yang Y, Repeta L, Feigon J. Structural basis for recognition of human 7SK long noncoding RNA by the La-related protein Larp7. Proc Natl Acad Sci U S A. 2018;115:E6457-E6466 pubmed publisher
    ..b>Larp7 binds to the abundant long noncoding 7SK RNA and is required for 7SK ribonucleoprotein (RNP) assembly and function...
  6. Stavraka C, Blagden S. The La-Related Proteins, a Family with Connections to Cancer. Biomolecules. 2015;5:2701-22 pubmed publisher
    ..La-related protein (LARP) family currently comprises Genuine La, LARP1, LARP1b, LARP4, LARP4b, LARP6 and LARP7. Emerging evidence suggests each LARP has a distinct role in transcription and/or mRNA translation that is ..
  7. Gao Z, Zhu X, Dou Y. The miR-302/367 cluster: a comprehensive update on its evolution and functions. Open Biol. 2015;5:150138 pubmed publisher
    ..distributed in vertebrates and occupies an intragenic cluster located in the gene La-related protein 7 (LARP7)...
  8. Hollink I, Alfadhel M, Al Wakeel A, Ababneh F, Pfundt R, De Man S, et al. Correction: Broadening the phenotypic spectrum of pathogenic LARP7 variants: two cases with intellectual disability, variable growth retardation and distinct facial features. J Hum Genet. 2018;63:539 pubmed publisher
    ..Correction to: Journal of Human Genetics (2016) 61, 229-33 https://doi.org/10.1038/jhg.2015.134 ; published online 26 November 2015. ..
  9. Eichhorn C, Chug R, Feigon J. hLARP7 C-terminal domain contains an xRRM that binds the 3' hairpin of 7SK RNA. Nucleic Acids Res. 2016;44:9977-9989 pubmed
    ..this domain contains an xRRM, a class of atypical RRM first identified in the Tetrahymena thermophila telomerase LARP7 protein p65...
  10. Xu L, Kong R, Zhu J, Sun H, Chang S. Unraveling the conformational determinants of LARP7 and 7SK small nuclear RNA by theoretical approaches. Mol Biosyst. 2016;12:2613-21 pubmed publisher
    b>LARP7, a member of the La-related proteins (LARPs), shares a conserved La module comprising the La-motif (LAM) and the RNA-recognition motif (RRM1), binding exclusively to the non-coding RNA 7SK...
  11. Xu J, Wang Y, Hua X, Xu J, Tian Z, Jin H, et al. Inhibition of PHLPP2/cyclin D1 protein translation contributes to the tumor suppressive effect of NF?B2 (p100). Oncotarget. 2016;7:34112-30 pubmed publisher
    ..Mechanistically, p100 inhibited Cyclin D1 protein translation by activating the transcription of LARP7 and its hosted miR-302d, which could directly bind to 3'-UTR of cyclin d1 mRNA and inhibited its protein ..
  12. Abasi M, Bazi Z, Mohammadi Yeganeh S, Soleimani M, Haghpanah V, Zargami N, et al. 7SK small nuclear RNA transcription level down-regulates in human tumors and stem cells. Med Oncol. 2016;33:128 pubmed
    ..MePCE), hexamethylene bisacetamide-inducible proteins 1 and 2 (HEXIM1 and HEXIM2) and La-related protein 7 (Larp7)...
  13. Hoodless L, Lucas C, Duffin R, Denvir M, Haslett C, Tucker C, et al. Genetic and pharmacological inhibition of CDK9 drives neutrophil apoptosis to resolve inflammation in zebrafish in vivo. Sci Rep. 2016;5:36980 pubmed publisher
    ..Importantly, knockdown of the negative regulator La-related protein 7 (LaRP7) increased neutrophilic inflammation...
  14. Li H, Lin S, Huang C, Lu F, Chiu P, Huang W, et al. miR-302 Attenuates Amyloid-β-Induced Neurotoxicity through Activation of Akt Signaling. J Alzheimers Dis. 2016;50:1083-98 pubmed publisher
    ..Furthermore, our in vivo studies revealed that the mRNA expression levels of both Nanog and miR-302-encoding LARP7 genes were significantly reduced in AD patients' blood cells, providing a novel diagnosis marker for AD...
  15. Nguyen D, Krueger B, Sedore S, Brogie J, Rogers J, Rajendra T, et al. The Drosophila 7SK snRNP and the essential role of dHEXIM in development. Nucleic Acids Res. 2012;40:5283-97 pubmed publisher
    ..In addition, a Drosophila La related protein (now called dLARP7) is shown to be the functional homolog of human LARP7. The Drosophila 7SK snRNP (d7SK snRNP) responded to treatment of cells with P-TEFb inhibitors and to nuclease ..
  16. Collopy L, Ware T, Goncalves T, Í Kongsstovu S, Yang Q, Amelina H, et al. LARP7 family proteins have conserved function in telomerase assembly. Nat Commun. 2018;9:557 pubmed publisher
    ..Here we have identified fission yeast Lar7 as a member of the conserved LARP7 family, which includes the Tetrahymena telomerase-binding protein p65 and human LARP7...
  17. Mennie A, Moser B, Nakamura T. LARP7-like protein Pof8 regulates telomerase assembly and poly(A)+TERRA expression in fission yeast. Nat Commun. 2018;9:586 pubmed publisher
    ..RNA for telomerase to function, and studies in Tetrahymena have established that p65, a La-related protein 7 (LARP7) family protein, utilizes its C-terminal xRRM domain to promote assembly of the telomerase ribonucleoprotein (RNP) ..
  18. Matrone G, Wilson K, Maqsood S, Mullins J, Tucker C, Denvir M. CDK9 and its repressor LARP7 modulate cardiomyocyte proliferation and response to injury in the zebrafish heart. J Cell Sci. 2015;128:4560-71 pubmed publisher
    ..In contrast, de-repression of Cdk9 activity, through knockdown of La-related protein (Larp7) increases phosphorylation of Ser2 in RNA polymerase II and increases cardiomyocyte proliferation...
  19. Hussain R, Zawawi M, Bayfield M. Conservation of RNA chaperone activity of the human La-related proteins 4, 6 and 7. Nucleic Acids Res. 2013;41:8715-25 pubmed publisher
  20. Slomnicki L, Malinowska A, Kistowski M, Palusiński A, Zheng J, Sepp M, et al. Nucleolar Enrichment of Brain Proteins with Critical Roles in Human Neurodevelopment. Mol Cell Proteomics. 2016;15:2055-75 pubmed publisher
    ..g. EMG1, RPL10, DKC1, EIF4A3, FLNA, SMC1, ATRX, MCM4, NSD1, LMNA, or CUL4B), others including ADAR, LARP7, GTF2I, or TCF4 have no such connections known...
  21. Brogie J, Price D. Reconstitution of a functional 7SK snRNP. Nucleic Acids Res. 2017;45:6864-6880 pubmed publisher
    ..We then used recombinant P-TEFb, HEXIM1, LARP7 and MEPCE to reconstruct a functional 7SK snRNP in vitro...
  22. Mizutani T, Ishizaka A, Suzuki Y, Iba H. 7SK small nuclear ribonucleoprotein complex is recruited to the HIV-1 promoter via short viral transcripts. FEBS Lett. 2014;588:1630-6 pubmed publisher
    ..This report provides insight into how 7SK snRNP complex is recruited to HIV-1 promoter in the absence of Tat. ..
  23. McNamara R, McCann J, Gudipaty S, D ORSO I. Transcription factors mediate the enzymatic disassembly of promoter-bound 7SK snRNP to locally recruit P-TEFb for transcription elongation. Cell Rep. 2013;5:1256-68 pubmed publisher
    ..Recruitment of PPM1G to promoter-assembled 7SK snRNP provides a paradigm for rapid gene activation through transcriptional pause release. ..
  24. Calo E, Flynn R, Martin L, Spitale R, Chang H, Wysocka J. RNA helicase DDX21 coordinates transcription and ribosomal RNA processing. Nature. 2015;518:249-53 pubmed publisher
    ..Our results uncover the multifaceted role of DDX21 in multiple steps of ribosome biogenesis, and provide evidence implicating a mammalian RNA helicase in RNA modification and Pol II elongation control. ..
  25. Warda A, Kretschmer J, Hackert P, Lenz C, Urlaub H, Hobartner C, et al. Human METTL16 is a N6-methyladenosine (m6A) methyltransferase that targets pre-mRNAs and various non-coding RNAs. EMBO Rep. 2017;18:2004-2014 pubmed publisher
    ..for N6-methylation of A43 of the U6 snRNA and identify the early U6 biogenesis factors La, LARP7 and the methylphosphate capping enzyme MEPCE as METTL16 interaction partners...
  26. Uchikawa E, Natchiar K, Han X, Proux F, Roblin P, Zhang E, et al. Structural insight into the mechanism of stabilization of the 7SK small nuclear RNA by LARP7. Nucleic Acids Res. 2015;43:3373-88 pubmed publisher
    ..The La-related protein LARP7 is a component of the 7SKsnRNP required for stability and function of the RNA...
  27. Nilson K, Price D. The Role of RNA Polymerase II Elongation Control in HIV-1 Gene Expression, Replication, and Latency. Genet Res Int. 2011;2011:726901 pubmed publisher
    ..HIV, the causative agent of AIDS, is a worldwide health concern. It is hoped that knowledge of the mechanisms regulating the expression of the HIV genome will lead to treatments and ultimately a cure. ..
  28. Egloff S, Vitali P, Tellier M, Raffel R, Murphy S, Kiss T. The 7SK snRNP associates with the little elongation complex to promote snRNA gene expression. EMBO J. 2017;36:934-948 pubmed publisher
    The 7SK small nuclear RNP (snRNP), composed of the 7SK small nuclear RNA (snRNA), MePCE, and Larp7, regulates the mRNA elongation capacity of RNA polymerase II (RNAPII) through controlling the nuclear activity of positive transcription ..
  29. Martinez Zapien D, Saliou J, Han X, Atmanene C, Proux F, Cianférani S, et al. Intermolecular recognition of the non-coding RNA 7SK and HEXIM protein in perspective. Biochimie. 2015;117:63-71 pubmed publisher
    A 7SKsnRNP complex, comprising the non-coding RNA 7SK and proteins MePCE and LARP7, participates in the regulation of the transcription elongation by RNA-polymerase II in higher eukaryotes...
  30. Mousseau G, Mediouni S, Valente S. Targeting HIV transcription: the quest for a functional cure. Curr Top Microbiol Immunol. 2015;389:121-45 pubmed publisher
    ..Finally, we discuss the impact of extracellular Tat in HIV-associated neurocognitive disorders and cancers. ..
  31. Ji X, Lu H, Zhou Q, Luo K. LARP7 suppresses P-TEFb activity to inhibit breast cancer progression and metastasis. elife. 2014;3:e02907 pubmed publisher
    ..A reservoir of P-TEFb is sequestered in the inactive 7SK snRNP where 7SK snRNA and the La-related protein LARP7 are required for the integrity of this complex...
  32. Taube R, Peterlin M. Lost in transcription: molecular mechanisms that control HIV latency. Viruses. 2013;5:902-27 pubmed publisher
  33. Wang W, Yao X, Huang Y, Hu X, Liu R, Hou D, et al. Mediator MED23 regulates basal transcription in vivo via an interaction with P-TEFb. Transcription. 2013;4:39-51 pubmed publisher
    ..Further, we demonstrate that MED23 interacts with CDK9 in vivo and in vitro. Collectively, these results provide the mechanistic insight into how Mediator promotes RNAP II into transcription elongation. ..
  34. Maraia R, Mattijssen S, Cruz Gallardo I, Conte M. The La and related RNA-binding proteins (LARPs): structures, functions, and evolving perspectives. Wiley Interdiscip Rev RNA. 2017;8: pubmed publisher
    ..We provide an overview of the high-resolution structural biology of La and LARPs. LARP7 family members most closely resemble La but function with a single RNAP III nuclear transcript, 7SK, or telomerase ..
  35. Eilebrecht S, Benecke B, Benecke A. 7SK snRNA-mediated, gene-specific cooperativity of HMGA1 and P-TEFb. RNA Biol. 2011;8:1084-93 pubmed publisher
    ..7SK RNA thus establishes gene-dependent plasticity between HMGA1 chromatin remodeling and transcription initiation and P-TEFb transcription elongation. ..
  36. Nekhai S, Kumari N, Dhawan S. Role of cellular iron and oxygen in the regulation of HIV-1 infection. Future Virol. 2013;8:301-311 pubmed
    ..We also propose key intracellular pathways that may be involved in regulating HIV-1 replication, via protein kinase complexes, CDK9/cyclin T1 and CDK 2/cyclin E, protein phosphatase-1 and other host factors. ..
  37. D ORSO I, Frankel A. RNA-mediated displacement of an inhibitory snRNP complex activates transcription elongation. Nat Struct Mol Biol. 2010;17:815-21 pubmed publisher
    ..Recruitment of an inhibitory snRNP complex at an early stage in the transcription cycle provides a new paradigm for controlling gene expression with a noncoding RNA. ..
  38. Holohan B, Kim W, Lai T, Hoshiyama H, Zhang N, Alazami A, et al. Impaired telomere maintenance in Alazami syndrome patients with LARP7 deficiency. BMC Genomics. 2016;17:749 pubmed
    ..Because human LARP7 is the most likely ortholog of the Tetrahymena p65 protein, which is required for telomerase activity in that ..
  39. Cheng Y, Jin Z, Agarwal R, Ma K, Yang J, Ibrahim S, et al. LARP7 is a potential tumor suppressor gene in gastric cancer. Lab Invest. 2012;92:1013-9 pubmed publisher
    ..frequent truncating mutations of the RNA-binding protein gene, La ribonucleoprotein domain family, member-7 (LARP7) in gastric cancers (GCs) with frequent microsatellite instability...
  40. Barboric M, Lenasi T. Kick-sTARting HIV-1 transcription elongation by 7SK snRNP deporTATion. Nat Struct Mol Biol. 2010;17:928-30 pubmed publisher
    ..The HIV-1 Tat protein promotes viral transcription elongation by recruiting P-TEFb to RNA element TAR on the viral mRNA. Recent work from D'Orso and Frankel uncovers unexpected aspects of this process. ..
  41. Yu M, Yang W, Ni T, Tang Z, Nakadai T, Zhu J, et al. RNA polymerase II-associated factor 1 regulates the release and phosphorylation of paused RNA polymerase II. Science. 2015;350:1383-6 pubmed publisher
    ..These findings reveal cooperativity among P-TEFb, PAF1C, and CDK12 in pausing release and Pol II CTD phosphorylation. ..