Adenosine causes read-through into the late region of the HPV16 genome in a guanosine-dependent manner

TY - JOUR

T1 - Adenosine causes read-through into the late region of the HPV16 genome in a guanosine-dependent manner

AU - Yu, Haoran

AU - Wu, Chengjun

AU - Nilsson, Kersti

AU - Kajitani, Naoko

AU - Schwartz, Stefan

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Adenosine plays an important role in cell death and differentiation as well as in tumorigenesis and the intra- and extra-cellular levels range from nanomolar to millimolar levels under various physiological or pathophysiological conditions. Here we report that adenosine can activate HPV16 late gene expression in a dose- and time-dependent manner, but only in the presence of guanosine. This activation occurred within hours after addition of the nucleosides and was primarily dependent on the ENT1 nucleoside transporter protein. Induction of HPV16 late gene expression was mainly the result of increased read-through at the early HPV16 polyadenylation signal into the late region of the HPV16 genome, thereby producing HPV16 late L2 mRNAs. The effect of guanosine and adenosine on HPV16 late gene expression was mediated by the increased binding to HPV16 mRNAs and nuclear export of the cellular HuR protein. Our results demonstrate that nucleosides can affect HPV16 gene expression.

AB - Adenosine plays an important role in cell death and differentiation as well as in tumorigenesis and the intra- and extra-cellular levels range from nanomolar to millimolar levels under various physiological or pathophysiological conditions. Here we report that adenosine can activate HPV16 late gene expression in a dose- and time-dependent manner, but only in the presence of guanosine. This activation occurred within hours after addition of the nucleosides and was primarily dependent on the ENT1 nucleoside transporter protein. Induction of HPV16 late gene expression was mainly the result of increased read-through at the early HPV16 polyadenylation signal into the late region of the HPV16 genome, thereby producing HPV16 late L2 mRNAs. The effect of guanosine and adenosine on HPV16 late gene expression was mediated by the increased binding to HPV16 mRNAs and nuclear export of the cellular HuR protein. Our results demonstrate that nucleosides can affect HPV16 gene expression.

KW - Adenosine

KW - ENT1

KW - HPV16

KW - HuR

KW - Nucleoside

KW - Papillomavirus

KW - Polyadenylation

KW - Purine

KW - Splicing

UR - http://www.scopus.com/inward/record.url?scp=85048497658&partnerID=8YFLogxK

U2 - 10.1016/j.virol.2018.05.019

DO - 10.1016/j.virol.2018.05.019

M3 - Article

C2 - 29864673

AN - SCOPUS:85048497658

VL - 521

SP - 1

EP - 19

JO - Virology

JF - Virology

SN - 1096-0341

ER -