Morpholino binds RNA, denying access to inhibitor complex

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Jon Moulton
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Morpholino binds RNA, denying access to inhibitor complex

The interferon-gamma-activated inhibitor of translation (GAIT) complex is involved in mediating the inflammation response of macrophages. GAIT is a heterotetrameric protein complex which includes a tRNA synthetase, GAPDH, NS1-associated protein-1 and a ribosomal protein. After exposure of human monocyte U937 cells to interferon-gamma, the GAIT complex binds to the 3’-UTR of some mRNA transcripts, inhibiting translation; by 24 hours after exposure to interferon-gamma, translation has returned to normal levels.

After electroporating a Morpholino oligo targeting the GAIT binding site into U937 cells, the cells no longer responded to interferon-gamma treatment by decreasing translation of the GAIT-target mRNA transcripts. Electroporation of a control Morpholino failed to relieve the cells from translation inhibition in response to interferon-gamma.

Mukhopadhyay R, Ray PS, Arif A, Brady AK, Kinter M, Fox PL. DAPK-ZIPK-L13a axis constitutes a negative-feedback module regulating inflammatory gene expression. Mol Cell. 2008 Nov 7;32(3):371-82.