Alternative Intronic Polyadenylation Generates the Interleukin-6 Trans-signaling Inhibitor sgp130-E10

Abstract

Background: Interleukin (IL)-6 trans-signaling is inhibited by naturally occurring soluble gp130 (sgp130) variants. Results: Alternative intronic polyadenylation in the gp130 gene creates the novel natural IL-6 trans-signaling inhibitor sgp130-E10. Conclusion: Alternative mRNA polyadenylation contributes to regulation of IL-6 trans-signaling intensity. Significance: This is the first report on a soluble isoform of the key cytokine co-receptor gp130 originating from alternative polyadenylation.

Cleavage factor 25 deregulation contributes to pulmonary fibrosis through alternative polyadenylation

“…PDGF, a potent growth factor that stimulates collagen synthesis and plays an essential role in fibrosis, can also be modulated by APA (23). Moreover, GP130 can generate a soluble isoform through intrinsic APA that inhibits IL-6 trans-signaling (24). Despite these findings, genome-wide alternative polyadenylation has not, to our knowledge, been reported in IPF.…”

The IL-6/gp130/STAT3 signaling axis: recent advances towards specific inhibition

“…Several soluble forms of gp130 occur naturally in the human blood, which are generated by differential mRNA splicing and alternative polyadenylation [14]. These Interleukin-6 classic and trans-signaling.…”

Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study

“…The soluble gp130 (sgp130) is a master regulator of cytokine-mediated inflammatory, regenerative, and proliferative effects [1][2][3]. Three main sgp130 isoforms, with molecular weights between 50 and 110 KDa, can be detected in the circulation: sgp130-RAPS [4], sgp130-E10 [5], and full length sgp130 [6] produced by alternative splicing, alternative intronic polyadenylation [5], and Members of the IMPROVE study group are listed below Supplementary information The online version of this article (https:// doi.org/10.1038/s41435-019-0090-z) contains supplementary material, which is available to authorized users.…”