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Gene Review

NSMF  -  NMDA receptor synaptonuclear signaling and...

Homo sapiens

Synonyms: HH9, NELF, Nasal embryonic LHRH factor, Nasal embryonic luteinizing hormone-releasing hormone factor
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Disease relevance of NELF


High impact information on NELF

  • NELF is composed of five polypeptides, the smallest of which is identical to RD, a putative RNA-binding protein of unknown function [6].
  • Transcription elongation by RNA polymerase II (RNAPII) is negatively regulated by the human factors DRB-sensitivity inducing factor (DSIF) and negative elongation factor (NELF) [2].
  • Chromatin immunoprecipitation reveals that recruitment of COBRA1 and the other NELF subunits to endogenous ERalpha-responsive promoters is greatly stimulated upon estrogen treatment [3].
  • We report that the chromatin-specific transcription elongation factor FACT functions in conjunction with the RNA polymerase II CTD kinase P-TEFb to alleviate transcription inhibition by DSIF (DRB sensitivity-inducing factor) and NELF (negative elongation factor) [7].
  • Depletion of a subunit of NELF by RNA interference enhances the junB mRNA level both before and after induction, indicating that DSIF- and NELF-mediated pausing contributes to the negative regulation of junB expression, not only by inducing RNAPII pausing before induction but also by attenuating transcription after induction [8].

Biological context of NELF

  • Mutation screening detected in a patient with IHH one novel heterozygous missense mutation (1438A>G, T480A) at the donor-splice site in exon 15 of NELF [1].
  • Four other novel SNPs (102C > T and 1029C > T within the coding region, and two IVS14+47C > T and IVS15+41G > A) were also identified in NELF [1].
  • Assembling EST clones, RACE, and sequencing showed that NELF mapped to 9q34.3 is composed of 16 exons and 15 introns with a 1,590-bp ORF encoding 530 amino acids [1].
  • Before induction by interleukin-6, RNAPII, DSIF, and NELF accumulate in the promoter-proximal region of junB, mainly at around position +50 from the transcription initiation site [8].
  • Phosphorylation of the CTD protects early elongation complexes from negative transcription elongation factors such as NELF, DSIF, and factor 2 [9].

Anatomical context of NELF

  • A 3.0-kb transcript is expressed most highly in the adult and fetal brain, testis, and kidney, indicating that NELF plays a role in the function of these tissues [1].
  • Furthermore, down-regulation of NELF on GnRH cells as they enter the telencephalon may allow GnRH cells to distinguish a different pathway(s) in the CNS (from those leading to olfactory regions) and thereby facilitate establishment of the appropriate adult-like GnRH distribution [10].
  • Within the CNS, cells in the cortex, hippocampus, thalamus and olfactory regions express NELF pre- and postnatally [11].

Associations of NELF with chemical compounds

  • Control of transcription elongation requires a complex interplay between the recently discovered positive transcription elongation factor b (P-TEFb) and negative transcription elongation factors, 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRB) sensitivity inducing factors (DSIF) and the negative elongation factor (NELF) [12].
  • Antisense experiments demonstrated that knock-down of NELF decreased olfactory axon outgrowth and GnRH neuronal migration [10].

Physical interactions of NELF

  • Negative elongation factor (NELF) is a human transcription factor complex that cooperates with DRB sensitivity-inducing factor (DSIF)/hSpt4-hSpt5 to repress elongation by RNA polymerase II (RNAPII) [13].

Regulatory relationships of NELF


Other interactions of NELF

  • BACKGROUND: The human Spt4/Spt5 complex, termed DRB-sensitivity inducing factor (DSIF) is a dual regulator of transcription that stimulates, or, when cooperating with negative elongation factor (NELF), represses RNA polymerase II (RNAPII) elongation [14].
  • NELF and EBF2 genes have been considered good candidates for HH and a large number of patients need to be studied to assess their contribution to reproductive function [15].

Analytical, diagnostic and therapeutic context of NELF


  1. Characterization of the human nasal embryonic LHRH factor gene, NELF, and a mutation screening among 65 patients with idiopathic hypogonadotropic hypogonadism (IHH). Miura, K., Acierno, J.S., Seminara, S.B. J. Hum. Genet. (2004) [Pubmed]
  2. Stimulation of RNA polymerase II elongation by hepatitis delta antigen. Yamaguchi, Y., Filipovska, J., Yano, K., Furuya, A., Inukai, N., Narita, T., Wada, T., Sugimoto, S., Konarska, M.M., Handa, H. Science (2001) [Pubmed]
  3. Attenuation of estrogen receptor alpha-mediated transcription through estrogen-stimulated recruitment of a negative elongation factor. Aiyar, S.E., Sun, J.L., Blair, A.L., Moskaluk, C.A., Lu, Y.Z., Ye, Q.N., Yamaguchi, Y., Mukherjee, A., Ren, D.M., Handa, H., Li, R. Genes Dev. (2004) [Pubmed]
  4. Dynamics of human immunodeficiency virus transcription: P-TEFb phosphorylates RD and dissociates negative effectors from the transactivation response element. Fujinaga, K., Irwin, D., Huang, Y., Taube, R., Kurosu, T., Peterlin, B.M. Mol. Cell. Biol. (2004) [Pubmed]
  5. Structural studies on the RNA-recognition motif of NELF E, a cellular negative transcription elongation factor involved in the regulation of HIV transcription. Rao, J.N., Neumann, L., Wenzel, S., Schweimer, K., R??sch, P., W??hrl, B.M. Biochem. J. (2006) [Pubmed]
  6. NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation. Yamaguchi, Y., Takagi, T., Wada, T., Yano, K., Furuya, A., Sugimoto, S., Hasegawa, J., Handa, H. Cell (1999) [Pubmed]
  7. FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and reveals functional differences between P-TEFb and TFIIH. Wada, T., Orphanides, G., Hasegawa, J., Kim, D.K., Shima, D., Yamaguchi, Y., Fukuda, A., Hisatake, K., Oh, S., Reinberg, D., Handa, H. Mol. Cell (2000) [Pubmed]
  8. Transcriptional pausing caused by NELF plays a dual role in regulating immediate-early expression of the junB gene. Aida, M., Chen, Y., Nakajima, K., Yamaguchi, Y., Wada, T., Handa, H. Mol. Cell. Biol. (2006) [Pubmed]
  9. C-terminal domain phosphatase sensitivity of RNA polymerase II in early elongation complexes on the HIV-1 and adenovirus 2 major late templates. Marshall, N.F., Dahmus, M.E. J. Biol. Chem. (2000) [Pubmed]
  10. Molecular mechanisms for migration of placodally derived GnRH neurons. Wray, S. Chem. Senses (2002) [Pubmed]
  11. Nasal embryonic LHRH factor (NELF) expression within the CNS and PNS of the rodent. Kramer, P.R., Wray, S. Brain Res. Gene Expr. Patterns (2001) [Pubmed]
  12. DSIF and NELF interact with RNA polymerase II elongation complex and HIV-1 Tat stimulates P-TEFb-mediated phosphorylation of RNA polymerase II and DSIF during transcription elongation. Ping, Y.H., Rana, T.M. J. Biol. Chem. (2001) [Pubmed]
  13. Evidence that negative elongation factor represses transcription elongation through binding to a DRB sensitivity-inducing factor/RNA polymerase II complex and RNA. Yamaguchi, Y., Inukai, N., Narita, T., Wada, T., Handa, H. Mol. Cell. Biol. (2002) [Pubmed]
  14. Structure-function analysis of human Spt4: evidence that hSpt4 and hSpt5 exert their roles in transcriptional elongation as parts of the DSIF complex. Kim, D.K., Inukai, N., Yamada, T., Furuya, A., Sato, H., Yamaguchi, Y., Wada, T., Handa, H. Genes Cells (2003) [Pubmed]
  15. Molecular analysis of KAL-1, GnRH-R, NELF and EBF2 genes in a series of Kallmann syndrome and normosmic hypogonadotropic hypogonadism patients. Trarbach, E.B., Baptista, M.T., Garmes, H.M., Hackel, C. J. Endocrinol. (2005) [Pubmed]
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