Disease relevance of NOLA1

• Determinants of the interaction of the spinal muscular atrophy disease protein SMN with the dimethylarginine-modified box H/ACA small nucleolar ribonucleoprotein GAR1 [1].

High impact information on NOLA1

• Here, we describe the 2.1 A crystal structure of a specific complex of three archaeal H/ACA proteins, Cbf5, Nop10, and Gar1 [2].
• In eukaryotes, two distinct classes of small nucleolar RNAs (snoRNAs), namely the fibrillarin-associated box C/D snoRNAs and the Gar1p-associated box H/ACA snoRNAs, direct the site-specific 2'-O-ribose methylation and pseudouridylation of ribosomal RNAs (rRNAs), respectively [3].
• Here we present results that indicate that the interaction of SMN with GAR1 is mediated by the Tudor domain of SMN [1].
• Furthermore, we find that either of the two arginine/glycine-rich domains of GAR1 can provide for interaction with SMN, but removal of both results in loss of the interaction [1].
• Single point mutations within the Tudor domain, including a spinal muscular atrophy patient mutation, impair the interaction of SMN with GAR1 [1].

Biological context of NOLA1

• Using PCR, RNA blot and genomic DNA analysis, we provide evidence that the beta subunit is produced from a complex locus on chromosome 16 which is also capable of generating independent transcripts corresponding to GAR1 and the C-terminal two-thirds of the beta subunit [4].
• Pretreatment with NOLA partially restored Ang II responses to postpartum levels [5].
• After NOLA, acetylcholine-induced vasodilatation in the collared vascular bed was no longer different from the vasodilatation in the control bed.(ABSTRACT TRUNCATED AT 250 WORDS)[6]
• 3. Oral NL-nitro-L-arginine (NOLA; 5 or 10 mg/kg) was given for 1 week in early (6-8 weeks gestation), middle (14-16 weeks gestation) and late (22-24 weeks gestation) pregnancy and while non-pregnant [7].

Anatomical context of NOLA1

• The survival of motor neurons (SMN) protein interacts with the snoRNP proteins fibrillarin and GAR1 [8].
• cDNA, gene structure, and chromosomal localization of human GAR1 (CNCG3L), a homolog of the third subunit of bovine photoreceptor cGMP-gated channel [9].
• PCR of somatic cell hybrid DNA with primer pairs that amplify a portion of the GAR1 gene (locus designation CNCG3L) demonstrate localization to chromosome 16 [9].

Associations of NOLA1 with chemical compounds

• GAR2, an aldehyde reductase, was also active in the reduction of D-glucose, with an apparent Km comparable to that of GAR1 but with a Vmax only 14% that of GAR1 [10].
• Sodium depletion also significantly reduced responses to Ang II by the same amount as in pregnancy, and these responses returned to normal with pretreatment with NOLA [5].
• Vascular NO production was inhibited by pretreatment with N omega-nitro-L-arginine (NOLA 10 mg/kg), a NO-synthase inhibitor [5].
• The vasodilator responses to intravenous infusions of the endothelium-dependent vasodilator, acetylcholine, and glyceryl trinitrate were measured in each artery at 2 and 7 days after surgical placement of the collar, and again following infusion of the nitric oxide synthase inhibitor, N-nitro-L-arginine (NOLA, 15 mg/kg) [6].
• Pretreatment with the cyclooxygenase inhibitor, indomethacin (1 microM) and the nitric oxide synthase inhibitor N(w)-nitro-L-arginine (NOLA, 100 microM) did not significantly affect either the EC(50) or the maximum contraction to ET-1 in veins from normal full-term and preterm preparations [11].

Other interactions of NOLA1

• Coimmunoprecipitations demonstrate that the SMN complex associates with fibrillarin and with GAR1 in vivo [8].

References