Retina International's Scientific Newsletter - Neuroretina-linked Leucine Zipper

	Retina International's Scientific Newsletter
Editor's Notes from literature on Neuroretina-linked Leucine Zipper (NRL)

Recent update from: 19.12.1999

NRL

Notes

Member of bZip protein sub-family
Binds AP1 and CRE sites, as well as AP1 site variants
Forms heterodimers with Fos and jun in vitro
Mutations in the leucine zipper dimerization interface or basic DNA contact region inhibits heterodimer formation and binding to the AP1 site
Dimerization juxtaposes basic regions in each protein to form a bimolecular contact surface
By extension of alpha-helices of the leucine zipper DNA is contacted in the major groove

Species:

See also:

Chromosomal localisation	in man:
	in mouse:

Gene Data

Exons:

Primers:

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE:
	calculated:

Reference: (3)

NRL

Notes

Strong homology with v-maf
bZip DNA protein
Responsive element TGCTGATCAGC in RHO
NRL transcativates RHO promoter
Photoreceptor specific but retina expression

Species:

See also:

Chromosomal localisation	in man:
	in mouse:

Gene Data

Exons:

Primers:

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE:
	calculated:

Reference: (6)

NRL

Notes

Binds to extended AP1 element as homo- and heterodimer = conserved NRL response element (NRE)
Positively regulates Rhodopsin
Binds region -61 - -84 of RHO promotor
Forms heterodimers with Maf and members of the c-Jun or c-Fos family
Consensus sequence is TGCN6-8GCA = NRE
Probably responsible for archieving stringently cell type- and developmental stage-specific expression
t-NRL may act as negative regulator of NRL function
NRE deletion reduces promotor activity

Species: Bos taurus

See also: RHO

Chromosomal localisation	in man:
	in mouse:

Gene Data

Exons:

Primers:

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE:
	calculated:

Reference: (4)

NRL

Notes

Transactivation domain rich in Pro, Ser and Thr in the first half of the protein (exon 2): AA 3 - 27/ 41-54
DNA-binding domain at the C-terminus
In all postmitotic neurons during mouse development
Adult expresssion restricted to retina

Species: Homo sapiens

See also:

Chromosomal localisation	in man:
	in mouse:

Gene Data

Exons:

Primers:

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE:
	calculated:

Reference: (1)

NRL

Notes

Close marker: D14S46E

Species: Homo sapiens

See also:

Chromosomal localisation	in man: 14q11.1-11.2
	in mouse:

Gene Data

cDNA:

Exons:

Primers:

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE:
	calculated:

Reference: (7)

NRL

Notes

Expressed in retina and retinoblastoma cell lines
Expression in man from ~ 7 months on
High expression in photoreceptors
Shows homology with jun and fos and v-maf
Consensus phosphorylation sites for PKA and proline-directed PK in the N-terminal region

Species: Homo sapiens

See also:

Chromosomal localisation	in man:
	in mouse:

Gene Data

mRNA: 1.3 kb

Exons:

Primers:

Protein Data

Aminoacids: 237 AA

Molecularweight	on SDS-PAGE: ~30 kDa
	calculated:

Reference: (5)

nrl

Notes

Various cDNAs due to alternate polyadenylation
Highly conserved between man and mouse
Polymorphic AGG repeat in 3' UTR
First exon is untranslated
No canonical TATA-box
Consensus binding sites for several DNA-binding proteins
cDNA
CCAAT-box, octamer motif, AP2-binding site, 2 E-boxes
Expressed only in retinal tissue and retinoblastoma cell lines
Genomic size: 6 kb

Species: Mus musculus

See also:

Chromosomal localisation	in man:
	in mouse:

Gene Data

cDNA:

Exons: 3

Primers:

Protein Data

Aminoacids: 237

Molecularweight	on SDS-PAGE:
	calculated:

Reference: (2)

References:

1. Bessant, D.A., Payne, A.M., Mitton, K.P., Wang, Q.L., Swain, P.K., Plant, C., Bird, A.C., Zack, D.J., Swaroop, A., and Bhattacharya, S.S. A mutation in NRL is associated with autosomal dominant retinitis pigmentosa. 1999; Nat.Genet. 21: 355 - 356.
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2. Farjo, Q., Jackson, A.U., Xu, J., Gryzenia, M., Skolnick, C., Agarwal, N., and Swaroop, A. Molecular characterization of the murine neural retina leucine zipper gene, Nrl. 1993; Genomics. 18: 216 - 222.
Goto Top

3. Kerppola, T.K. and Curran, T. Maf and Nrl can bind to AP-1 sites and form heterodimers with Fos and Jun. 1994; Oncogene. 9: 675 - 684.
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4. Rehemtulla, A., Warwar, R., Kumar, R., Ji, X., Zack, D.J., and Swaroop, A. The basic motif-leucine zipper transcription factor Nrl can positively regulate rhodopsin gene expression. 1996; Proc.Natl.Acad.Sci.U.S.A. 93: 191 - 195.
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5. Swaroop, A., Xu, J.Z., Pawar, H., Jackson, A., Skolnick, C., and Agarwal, N. A conserved retina-specific gene encodes a basic motif/leucine zipper domain. 1992; Proc.Natl.Acad.Sci.U.S.A. 89: 266 - 270.
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6. Warwar, R., Rehemtulla, A., Kumar, R., Ji, X., Zack, D., and Swaroop, A. The bZIP transcription factor NRL is involved in regulating rhodopsin gene expression. 1995; Invest.Ophthalmol.Vis.Sci. 36: S430
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7. Yang Feng, T.L. and Swaroop, A. Neural retina-specific leucine zipper gene NRL (D14S46E) maps to human chromosome 14q11.1-q11.2. 1992; Genomics. 14: 491 - 492.
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Contact the editor: irpamp@irpa.org	This site is maintained and edited by Dr. rer. medic. Markus Preising, Dipl.Biol. Molecular Genetics Laboratory Department of Paediatric Ophthalmology, Strabismology and Ophthalmogenetics University of Regensburg Head: Prof. Dr. med. Birgit Lorenz