Regnase-1, a rapid response ribonuclease regulating inflammation and stress responses

Renfang Mao, Riyun Yang, Xia Chen, Edward W. Harhaj, Xiaoying Wang, Yihui Fan

Research output: Research - peer-reviewReview article

Abstract

RNA-binding proteins (RBPs) are central players in post-transcriptional regulation and immune homeostasis. The ribonuclease and RBP Regnase-1 exerts critical roles in both immune cells and non-immune cells. Its expression is rapidly induced under diverse conditions including microbial infections, treatment with inflammatory cytokines and chemical or mechanical stimulation. Regnase-1 activation is transient and is subject to negative feedback mechanisms including proteasome-mediated degradation or mucosa-associated lymphoid tissue 1 (MALT1) mediated cleavage. The major function of Regnase-1 is promoting mRNA decay via its ribonuclease activity by specifically targeting a subset of genes in different cell types. In monocytes, Regnase-1 downregulates IL-6 and IL-12B mRNAs, thus mitigating inflammation, whereas in T cells, it restricts T-cell activation by targeting c-Rel, Ox40 and Il-2 transcripts. In cancer cells, Regnase-1 promotes apoptosis by inhibiting anti-apoptotic genes including Bcl2L1, Bcl2A1, RelB and Bcl3. Together with up-frameshift protein-1 (UPF1), Regnase-1 specifically cleaves mRNAs that are active during translation by recognizing a stem-loop (SL) structure within the 3′UTRs of these genes in endoplasmic reticulum-bound ribosomes. Through this mechanism, Regnase-1 rapidly shapes mRNA profiles and associated protein expression, restricts inflammation and maintains immune homeostasis. Dysregulation of Regnase-1 has been described in a multitude of pathological states including autoimmune diseases, cancer and cardiovascular diseases. Here, we provide a comprehensive update on the function, regulation and molecular mechanisms of Regnase-1, and we propose that Regnase-1 may function as a master rapid response gene for cellular adaption triggered by microenvironmental changes.

LanguageEnglish (US)
Pages412-422
Number of pages11
JournalCellular and Molecular Immunology
Volume14
Issue number5
DOIs
StatePublished - May 1 2017

Fingerprint

Ribonucleases
Inflammation
Genes
Messenger RNA
RNA-Binding Proteins
Homeostasis
T-Lymphocytes
Neoplasms
Proteins
RNA Stability
3' Untranslated Regions
Lymphoid Tissue
Proteasome Endopeptidase Complex
Ribosomes
Endoplasmic Reticulum
Autoimmune Diseases
Monocytes
Interleukin-6
Mucous Membrane
Cardiovascular Diseases

Keywords

  • Autoimmune diseases
  • microenvironment
  • Regnase-1
  • ribonuclease
  • RNA-binding proteins

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Regnase-1, a rapid response ribonuclease regulating inflammation and stress responses. / Mao, Renfang; Yang, Riyun; Chen, Xia; Harhaj, Edward W.; Wang, Xiaoying; Fan, Yihui.

In: Cellular and Molecular Immunology, Vol. 14, No. 5, 01.05.2017, p. 412-422.

Research output: Research - peer-reviewReview article

Mao, Renfang ; Yang, Riyun ; Chen, Xia ; Harhaj, Edward W. ; Wang, Xiaoying ; Fan, Yihui. / Regnase-1, a rapid response ribonuclease regulating inflammation and stress responses. In: Cellular and Molecular Immunology. 2017 ; Vol. 14, No. 5. pp. 412-422
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