Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Editorial
. 2018;17(4):407-409.
doi: 10.1080/15384101.2018.1429082. Epub 2018 Apr 3.

Chronic innate immune signaling results in ubiquitination of splicing machinery

Ashley E Culver-Cochran  1 , Daniel T Starczynowski  1   2
Affiliations
Editorial

Chronic innate immune signaling results in ubiquitination of splicing machinery

Ashley E Culver-Cochran et al. Cell Cycle. 2018.
No abstract available

Keywords: RNA splicing; TRAF6, hematopoiesis; immune biology; innate immune signaling; myelodysplastic syndrome (MDS).

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Overview of isoform usage in response to transient (left) or chronic TLR signaling (right). During a normal immune response, TRAF6 transiently catalyzes K63-linked ubiquitin (Ub) chains on RNA binding proteins, like hnRNPA1, which leads to differential splicing of target genes, such as Arhgap, and an appropriate balance of isoform expression. Chronic TLR activation results in TRAF6 overexpression and continuous ubiquitination of hnRNPA1 (1), which leads to skewed isoform usage of Arhgap (2) and subsequent alteration of downstream signaling pathways (3), such as the one involving the small G-protein GTPase Cdc42. Overactive Cdc42 signaling contributes to HSPC defects and myelodysplasia associated with bone marrow failure. Transcription of alternatively spliced genes was not exclusively driven by NF-κB and likely involves other transcription factors (TF). NF-κB signaling was not hyperactive following TRAF6 overexpression (indicated in grey).
See this image and copyright information in PMC

Comment on

References

    1. Varney ME, Niederkorn M, Konno H, et al. . . Loss of Tifab, a del(5q) MDS gene, alters hematopoiesis through derepression of Toll-like receptor–TRAF6 signaling. J Exp Med. 2015;212(11):1967–1985. doi:10.1084/jem.20141898. PMID:26458771. - DOI - PMC - PubMed
    1. Varney ME, Choi K, Bolanos L, et al. . . Epistasis between TIFAB and miR-146a: neighboring genes in del(5q) myelodysplastic syndrome. Leukemia. 2017;31(7):1659. doi:10.1038/leu.2017.95. PMID:28386122. - DOI - PMC - PubMed
    1. Fang J, Bolanos LC, Choi K, et al. . . Corrigendum: Ubiquitination of hnRNPA1 by TRAF6 links chronic innate immune signaling with myelodysplasia. Nat Immunol. 2017;18(4):474. doi:10.1038/ni0417-474a PMID:28323261 - DOI - PMC - PubMed
    1. Bellare P, Small EC, Huang X, et al. . . A role for ubiquitin in the spliceosome assembly pathway. Nat Struct Mol Biol. 2008;15(5):444–451. doi:10.1038/nsmb.1401. PMID:18425143. - DOI - PMC - PubMed
    1. Florian MC, Dörr K, Niebel A, et al. . Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation . Cell Stem Cell. 2012;10(5):520–530. doi:10.1016/j.stem.2012.04.007. PMID:22560076. - DOI - PMC - PubMed

Substances