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Endogenous double-stranded RNA

Lookup NU author(s): Dr Dr Shaymaa Sadeq, Dr Surar Al-Hashimi, Carmen Cusack, Dr Andreas Werner



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2021 by the authors. Licensee MDPI, Basel, Switzerland. The birth of long non-coding RNAs (lncRNAs) is closely associated with the presence and activation of repetitive elements in the genome. The transcription of endogenous retroviruses as well as long and short interspersed elements is not only essential for evolving lncRNAs but is also a significant source of double-stranded RNA (dsRNA). From an lncRNA-centric point of view, the latter is a minor source of bother in the context of the entire cell; however, dsRNA is an essential threat. A viral infection is associated with cytoplasmic dsRNA, and endogenous RNA hybrids only differ from viral dsRNA by the 5′ cap structure. Hence, a multi-layered defense network is in place to protect cells from viral infections but tolerates endogenous dsRNA structures. A first line of defense is established with compartmentalization; whereas endogenous dsRNA is found predominantly confined to the nucleus and the mitochondria, exogenous dsRNA reaches the cytoplasm. Here, various sensor proteins recognize features of dsRNA including the 5′ phosphate group of viral RNAs or hybrids with a particular length but not specific nucleotide sequences. The sensors trigger cellular stress pathways and innate immunity via interferon signaling but also induce apoptosis via caspase activation. Because of its central role in viral recognition and immune activation, dsRNA sensing is implicated in autoimmune diseases and used to treat cancer.

Publication metadata

Author(s): Sadeq S, Al-Hashimi S, Cusack CM, Werner A

Publication type: Article

Publication status: Published

Journal: Non-Coding RNA

Year: 2021

Volume: 7

Issue: 1

Online publication date: 19/02/2021

Acceptance date: 17/02/2021

Date deposited: 04/06/2021

ISSN (electronic): 2311-553X

Publisher: MDPI AG


DOI: 10.3390/ncrna7010015


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Funder referenceFunder name
18.011Northern Counties Kidney Research Fund