Identification of a subnuclear body involved in sequence-specific cytokine RNA processing.

Abstract:

:Processing of interleukin RNAs must be tightly controlled during the immune response. Here we report that a subnuclear body called the interleukin-6 and -10 splicing activating compartment (InSAC) is a nuclear site of cytokine RNA production and stability. Tat-activating regulatory DNA-binding protein-43 (TDP-43) acts as an InSAC scaffold that selectively associates with IL-6 and IL-10 RNAs in a sequence-specific manner. TDP-43 also recruits key spliceosomal components from Cajal bodies. LPS induces posttranslational modifications of TDP-43; in particular, TDP-43 ubiquitination provides a driving force for InSAC formation. As a consequence, in vivo depletion of TDP-43 leads to a dramatic reduction in the RNA processing and the protein levels of IL-6 in serum. Collectively, our findings highlight the importance of TDP-43-mediated InSAC biogenesis in immune regulation.

journal_name

Nat Commun

journal_title

Nature communications

authors

Lee S,Lee TA,Lee E,Kang S,Park A,Kim SW,Park HJ,Yoon JH,Ha SJ,Park T,Lee JS,Cheon JH,Park B

doi

10.1038/ncomms6791

subject

Has Abstract

pub_date

2015-01-05 00:00:00

pages

5791

issn

2041-1723

pii

ncomms6791

journal_volume

6

pub_type

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