A microRNA generated via lysosomal processing of ribosomal RNA suppresses proinflammatory responses.

Authors

Dan Michael, Ester Feldmesser, K Shanmugha Rajan, Yoav Lubelsky, Anat Bashan, Alexandros Damalas, Shiri Ben Zvi, Aya Friedberg, Netta Eitan, Shachar Erez, Ada Yonath, Igor Ulitsky, Moshe Oren

Published in

Life science alliance. Volume 9. Issue 7. Epub May 04, 2026.

Abstract

ER stress underlies numerous severe pathologies. We have metabolically perturbed normal fibroblasts to study the biological roles of microRNAs (miRs) under mild and extended ER stress. We now report that miR-4488 quenches inflammation-associated gene expression in such metabolically perturbed cells. Remarkably, generation of miR-4488 is Drosha-independent. Furthermore, we define miR-4488 as a noncanonical miRNA derived from the expansion segment ES7L of the 28S ribosomal RNA. Moreover, its generation involves the autophagy-lysosome route and is inhibited when this pathway is blocked, thus unveiling an anti-inflammatory role for ribosomal RNA and lysosomes, engaged at the onset of stress. Mechanistically, miR-4488 suppresses the expression of NFKB2 and RELB, whose mRNAs specifically associate with miR-4488 exclusively upon stress. This selectivity suggests that miR-4488 may bear promise for treating mild ER stress-associated diseases.

PMID:
42082377
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.

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