6/7 The STAT3 binding site in NORAD is located near an Alu element, which is conserved only in primates that have Alu in NORAD.
We propose that the introduction of an Alu into NORAD enabled its ability to bind STAT3, granting it a novel function in antiviral defense.

5/7 Interestingly, while the other functions of NORAD are conserved, we found no interaction between NORAD and STAT3 in mouse cells and no immune response upon NORAD knockdown in mice.

4/7 We discovered that NORAD levels decrease upon viral infection (SINV, SARS-CoV-2, HSV1, and IAV) in cell culture and in COVID-19 patients, and NORAD shows an inverse relation with the activation of the Interferon pathway.

3/7 STAT3 binds to the promoters of interferon-stimulated genes (ISGs) and inhibits their transcription.
In the absence of NORAD, STAT3 exits the nucleus, allowing STAT1 to bind in its place and activate the antiviral response.

2/7 In our previous paper, we found that the STAT3 interacts with RNA in hESCs and directly binds NORAD lncRNA, already known for its role in genome stability.
In this paper, we further investigate this interaction and reveal that NORAD is required for STAT3 nuclear localization.

1/7 I’m excited to share our paper, describing the majority of my PhD, now published in
@naturecomms.bsky.social
!
We present how the lncRNA NORAD interacts with STAT3 to regulate the antiviral response in human cells. A 🧵

www.nature.com/articles/s41...