Duf89 abets lncRNA control of fission yeast phosphate homeostasis via its antagonism of precocious lncRNA transcription termination.
Fission yeast phosphate homeostasis gene  pho1  is actively repressed during growth in phosphate-rich medium by transcription in  cis  of a long noncoding (lnc) RNA from the 5' flanking  prt(nc-pho1)  gene. Pho1 expression is: (i) derepressed by genetic maneuvers that favor precocious lncRNA 3'-processing and termination, in response to DSR and PAS signals in  prt ; and (ii) hyperrepressed in genetic backgrounds that dampen 3'-processing/termination efficiency. Governors of 3'-processing/termination include the RNA polymerase CTD code, the CPF (cleavage and polyadenylation factor) complex, termination factors Seb1 and Rhn1, and the inositol pyrophosphate signaling molecule 1,5-IP 8  Here, we present genetic and biochemical evidence that fission yeast Duf89, a metal-dependent phosphatase/pyrophosphatase, is an antagonist of precocious 3'-processing/termination. We show that derepression of  pho1  in  duf89 Δ cells correlates with squelching the production of full-length  prt  lncRNA and is erased or attenuated by: (i) DSR/PAS mutations in  prt ; (ii) loss-of-function mutations in components of the 3'-processing and termination machinery; (iii) elimination of the CTD Thr4-PO 4  mark; (iv) interdicting CTD prolyl isomerization by Pin1; (v) inactivating the Asp1 kinase that synthesizes IP 8 ; and (vi) loss of the putative IP 8  sensor Spx1. The findings that  duf89 Δ is synthetically lethal with  pho1 -derepressive mutations  CTD-S7A  and  aps1 Δ-and that this lethality is rescued by  CTD-T4A , CPF/Rhn1/Pin1 mutations, and  spx1 Δ-implicate Duf89 more broadly as a collaborator in cotranscriptional regulation of essential fission yeast genes. The  duf89-D252A  mutation, which abolishes Duf89 phosphohydrolase activity, phenocopied  duf89   + , signifying that  duf89 Δ phenotypes are a consequence of Duf89 protein absence, not absence of Duf89 catalysis.
Sanchez AM, Garg A, Schwer B, Shuman S