Pre-mRNA splicing is modulated by antifungal drugs in the filamentous fungus Neurospora crassa

FEBS Open Bio. 2016 Mar 14;6(4):358-68. doi: 10.1002/2211-5463.12047. eCollection 2016 Apr.

Abstract

For this study, we sought to identify pre-mRNA processing events modulated by changes in extracellular pH, inorganic phosphate, and antifungal drugs. We examined genes with at least four putative introns whose transcriptional level responded to these effectors. We showed that the intron retention levels of genes encoding asparagine synthetase 2, C6-zinc finger regulator (fluffy), and a farnesyltransferase respond to amphotericin B, ketoconazole, and other effectors. In general, the assayed antifungals promoted the disruption of the structural domains of these proteins probably leading to their inactivation, which emphasize the complexity of the metabolic modulation exerted by antifungal signaling.

Keywords: Neurospora crassa; Pi regulation; alternative splicing; amphotericin B; asparagine synthetase; intron retention; ketoconazole.