Title:Cellular Selenoprotein mRNA Tethering via Antisense Interactions with Ebola and HIV-1 mRNAs May Impact Host Selenium Biochemistry
Volume: 16
Issue: 13
Author(s): Ethan Will Taylor, Jan A. Ruzicka, Lakmini Premadasa and Lijun Zhao
Affiliation:
Keywords:
Antisense, Ebola, mRNA, Selenium, Selenoprotein, HIV, Tethering, Thioredoxin reductase
Abstract: Regulation of protein expression by non-coding RNAs typically involves effects on mRNA
degradation and/or ribosomal translation. The possibility of virus-host mRNA-mRNA antisense tethering
interactions (ATI) as a gain-of-function strategy, via the capture of functional RNA motifs, has
not been hitherto considered. We present evidence that ATIs may be exploited by certain RNA viruses
in order to tether the mRNAs of host selenoproteins, potentially exploiting the proximity of a captured
host selenocysteine insertion sequence (SECIS) element to enable the expression of virally-encoded selenoprotein modules,
via translation of in-frame UGA stop codons as selenocysteine. Computational analysis predicts thermodynamically
stable ATIs between several widely expressed mammalian selenoprotein mRNAs (e.g., isoforms of thioredoxin reductase)
and specific Ebola virus mRNAs, and HIV-1 mRNA, which we demonstrate via DNA gel shift assays. The probable functional
significance of these ATIs is further supported by the observation that, in both viruses, they are located in close
proximity to highly conserved in-frame UGA stop codons at the 3′ end of open reading frames that encode essential viral
proteins (the HIV-1 nef protein and the Ebola nucleoprotein). Significantly, in HIV/AIDS patients, an inverse correlation
between serum selenium and mortality has been repeatedly documented, and clinical benefits of selenium in the context of
multi-micronutrient supplementation have been demonstrated in several well-controlled clinical trials. Hence, in the light
of our findings, the possibility of a similar role for selenium in Ebola pathogenesis and treatment merits serious investigation.
