Inactivation of fission yeast Erh1 de-represses  pho1  expression: evidence that Erh1 is a negative regulator of  prt  lncRNA termination.
Fission yeast Erh1 exists in a complex with RNA-binding protein Mmi1. Deletion of  erh1  up-regulates the phosphate homeostasis gene  pho1 , which is normally repressed by transcription in  cis  of a 5' flanking  prt  lncRNA. Here we present evidence that de-repression of  pho1  by e rh1 Δ is achieved through precocious 3'-processing/termination of  prt  lncRNA synthesis, to wit: (i)  erh1 Δ does not affect the activity of the  prt  or  pho1  promoters per se; (ii) de-repression by  erh1 Δ depends on CPF (cleavage and polyadenylation factor) subunits Ctf1, Dis2, Ssu72, Swd22, and Ppn1 and on termination factor Rhn1; (iii) de-repression requires synthesis by the Asp1 IPP kinase of inositol 1-pyrophosphates (1-IPPs); (iv) de-repression is effaced by mutating Thr4 of the RNA polymerase II CTD to alanine; and (v)  erh1 Δ exerts an additive effect on  pho1  de-repression in combination with mutating CTD Ser7 to alanine and with deletion of the IPP pyrophosphatase Aps1. These findings point to Erh1 as an antagonist of lncRNA termination in the  prt-pho1  axis. In contrast, in  mmi1 Δ cells there is a reduction in  pho1  mRNA and increase in the formation of a  prt-pho1  read-through transcript, consistent with Mmi1 being an agonist of  prt  termination. We envision that Erh1 acts as a brake on Mmi1's ability to promote CPF-dependent termination during  prt  lncRNA synthesis. Consistent with this idea,  erh1 Δ de-repression of  pho1  was eliminated by mutating the Mmi1-binding sites in the  prt  lncRNA.
Schwer B, Sanchez AM, Shuman S