Truncated IFI16 mRNA transcripts can control its viral DNA defense activity

Abstract

One of the most well-known viral receptors of the group called named ALRs is IFI16 (interferon-inducible protein 16) that are responsible for responses against viral dsDNA. A pyrin domain (PYD), two HIN domains, a NLS (nuclear localization sequence), and S/T/P repeats region form the structure of IFI16. Five alternatively transcripts have been described (V1, V2, V9, V4 and Vβ) that encode five isoforms (IFI16-iso1, 2, 3, 4 and β) with different structure, localization, and function. Another four transcripts (V3, V5, V6, and V8) and 12 predicted transcripts (VX1-VX7, VX1.1-VX5.1) have also been registered in the Genebank without any structural study. In the present study, we have performed a complete study of the presence of the IFI16 transcripts in a healthy population. All the alternative transcripts described except six of the so-called predicted transcripts were found, furthermore, two new transcripts (V10, V11) were described. The main mechanisms for the regulation of mRNA from IFI16 expression are due to the insertion of non-coding regions and the loss of almost all exons. A total of nine different isoforms were found and the corresponding protein models were constructed to establish the modification of its functionality to form inflammasomes or the binding to viral DNA.