Rabbit Anti-Human ABCF1 (C-terminal) Polyclonal antibody

The inflammatory cytokine pathway may be a potential therapeutic target for major depressive disorder (MDD). Previous reports suggest that antidepressants have anti-inflammatory properties and can cause a reduction in proinflammatory cytokines. Recent evidence suggests this might be mediated at the level of the transcriptome. The current study investigated the transcription of 86 genes in the inflammatory cytokine pathway both at baseline and after eight weeks of escitalopram treatment in MDD patients who were either clinical responders (n=25) or non-responders (n=21), using a subset of samples in the Genome-Based Therapeutic Drugs for Depression project (GENDEP). Changes in expression between baseline and eight weeks of treatment were assessed using two-tailed t-tests. To establish if any significant expression changes related to clinical response, the magnitude of the relative expression change between baseline and eight weeks of treatment was established and binary logistic regressions were used to compare differences between responders and non-responders. ATP-binding cassette sub-family F member 1 (ABCF1), a translational regulator of the inflammatory cytokine pathway showed a significant increase in expression after escitalopram treatment which was significantly greater in responders compared to non-responders, suggesting that ABCF1 may play a role in mediating antidepressant response.

In eukaryotic cells, protein synthesis typically begins with the binding of eIF4F to the 7-methylguanylate (m(7)G) cap found on the 5' end of the majority of mRNAs. Surprisingly, overall translational output remains robust under eIF4F inhibition. The broad spectrum of eIF4F-resistant translatomes is incompatible with cap-independent translation mediated by internal ribosome entry sites (IRESs). Here, we report that N-6-methyladenosine (m(6)A) facilitates mRNA translation that is resistant to eIF4F inactivation. Depletion of the methyltransferase METTL3 selectively inhibits translation of mRNAs bearing 5' UTR methylation, but not mRNAs with 5' terminal oligopyrimidine (TOP) elements. We identify ABCF1 as a critical mediator of m(6)A-promoted translation under both stress and physiological conditions. Supporting the role of ABCF1 in m(6)A-facilitated mRNA translation, ABCF1-sensitive transcripts largely overlap with METTL3-dependent mRNA targets. By illustrating the scope and mechanism of eIF4F-independent mRNA translation, these findings reshape our current perceptions of cellular translational pathways.