Heg lnc RNA and Cdk1 mRNA in mononuclear cells and regulation of autoantibody levels

Abstract

We found some years ago an unknow non‒coding RNA fragment in mononuclear cells designated Heg lnc RNA (European Nucleotide Archive: EU137727.1).1,2 Heg RNA was located to chromosome 1, antisense to and overlaps a larger part of exon 7 from Nucks mRNA. Nucks (nuclear ubiquitous casein kinase and cyclin‒dependent substrate) plays a major role in the regulation of transcription and is a substrate for Cdk1. Heg and other RNA products were quantified by RT‒PCR‒HPLC.1 The mean concentration of Heg lnc RNA in normal subjects were 0.15±0.01 amol/μg of DNA.2 Surprisingly we found that Heg lnc RNA was close and negatively correlated with concentrations of TSH receptor autoantibodies (TRAb) in patients with untreated Graves disease. We also study Cdk1 and CK2 mRNAs (homo sapiens casein kinase I and II), which both are members of the cyclin‒ dependent kinase cascade. Cdk1 is important for cell division and differentiation.3 Cdk1 was positively correlated with concentrations of TRAb, but only provided Heg was included in the analysis. We did not find other RNA fragments, which correlated with TRAb. The interaction between Heg lnc RNA and Cdk1 mRNA explained a large and high significant part of the variation in TRAb. It is easy to understand why Cdk1, which regulates cell cycle, correlates with TRAb. The mechanism of action for Heg, on the other hand, is not known. Heg may reflect effects of Nucks, but there was no correlation between Nucks and TRAb. Gene expression in mononuclear cells after incubation for 20 hours led to the expected increase in GCR and NF‒kB mRNAs, whereas Heg, Nucks mRNA and Cd14 mRNA were only slightly changed. A general inhibition of gene expression reduced the concentration of both Nucks mRNA and Heg significant.