Toll/interleukin-1 receptor (TIR) domain-containing proteins have NAD-RNA decapping activity

© 2024. The Author(s)..

The occurrence of NAD+ as a non-canonical RNA cap has been demonstrated in diverse organisms. TIR domain-containing proteins present in all kingdoms of life act in defense responses and can have NADase activity that hydrolyzes NAD+. Here, we show that TIR domain-containing proteins from several bacterial and one archaeal species can remove the NAM moiety from NAD-capped RNAs (NAD-RNAs). We demonstrate that the deNAMing activity of AbTir (from Acinetobacter baumannii) on NAD-RNA specifically produces a cyclic ADPR-RNA, which can be further decapped in vitro by known decapping enzymes. Heterologous expression of the wild-type but not a catalytic mutant AbTir in E. coli suppressed cell propagation and reduced the levels of NAD-RNAs from a subset of genes before cellular NAD+ levels are impacted. Collectively, the in vitro and in vivo analyses demonstrate that TIR domain-containing proteins can function as a deNAMing enzyme of NAD-RNAs, raising the possibility of TIR domain proteins acting in gene expression regulation.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:15

Enthalten in:

Nature communications - 15(2024), 1 vom: 13. März, Seite 2261

Sprache:

Englisch

Beteiligte Personen:

Wang, Xufeng [VerfasserIn]
Yu, Dongli [VerfasserIn]
Yu, Jiancheng [VerfasserIn]
Hu, Hao [VerfasserIn]
Hang, Runlai [VerfasserIn]
Amador, Zachary [VerfasserIn]
Chen, Qi [VerfasserIn]
Chai, Jijie [VerfasserIn]
Chen, Xuemei [VerfasserIn]

Links:

Volltext

Themen:

0U46U6E8UK
Journal Article
NAD
RNA Caps
Receptors, Interleukin-1

Anmerkungen:

Date Completed 15.03.2024

Date Revised 17.03.2024

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41467-024-46499-y

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369704193