Flavivirus infection causes host cell death by initiation of an unfolded protein 
response (UPR). UPR is initiated following activation of three ER-membrane 
resident sensors, PERK, IRE1α and ATF6, which are otherwise kept inactive 
through association with the ER-chaperone GRP78. Activation precedes cellular 
and molecular changes that act to restore homeostasis but might eventually 
initiate apoptosis. These changes involve influencing function of multiple genes 
by either transcriptional or post-transcriptional or post-translational 
mechanisms. Transcriptional control includes expression of transcription factor 
cascades, which influence cognate gene expression. Malat1 is a long non-coding 
RNA which is over-expressed in many human oncogenic tissues and regulates cell 
cycle and survival. In this report, for the first time we show activation of 
Malat1 following infection by two flaviviruses, both of which activate the UPR 
in host cells. The temporal kinetics of expression was restricted to later time 
points. Further, Malat1 was also activated by pharmacological inducer of UPR, to 
a similar degree. Using drugs that specifically inhibit or activate the PERK or 
IRE1α sensors, we demonstrate that signalling through the PERK axis activates 
this expression, through a transcriptional mechanism. To our knowledge, this is 
the first report of an UPR pathway regulating the expression of an lncRNA.