biostudies-literatureSchwer BHHS | NIH | National Institute of General Medical SciencesNCI NIH HHSNIGMS NIH HHSNIH HHSe2108105118https://www.ebi.ac.uk/biostudies/studies/S-EPMC8379984biostudies-literatureUnknown118(33)The system of long noncoding RNA (lncRNA)-mediated transcriptional interference that represses fission yeast phosphate homoeostasis gene <i>pho1</i> provides a sensitive readout of genetic influences on cotranscriptional 3'-processing and termination and a tool for discovery of regulators of this phase of the Pol2 transcription cycle. Here, we conducted a genetic screen for relief of transcriptional interference that unveiled a mechanism by which Pol2 termination is enhanced via a gain-of-function mutation, G476S, in the RNA-binding domain of an essential termination factor, Seb1. The genetic and physical evidence for gain-of-function is compelling: 1) <i>seb1-G476S</i> de-represses <i>pho1</i> and <i>tgp1</i>, both of which are subject to lncRNA-mediated transcriptional interference; 2) <Proceedings of the National Academy of Sciences of the United States of AmericaGenetic screen for suppression of transcriptional interference identifies a gain-of-function mutation in Pol2 termination factor Seb1.PMC8379984R35 GM126945P30 CA008748P30 GM124165S10 OD021527R35-GM126945R01-GM134021R01 GM134021Schwer BShuman SGarg AJacewicz AfalseGenetic screen for suppression of transcriptional interference identifies a gain-of-function mutation in Pol2 termination factor Seb1.The system of long noncoding RNA (lncRNA)-mediated transcriptional interference that represses fission yeast phosphate homoeostasis gene <i>pho1</i> provides a sensitive readout of genetic influences on cotranscriptional 3'-processing and termination and a tool for discovery of regulators of this phase of the Pol2 transcription cycle. Here, we conducted a genetic screen for relief of transcriptional interference that unveiled a mechanism by which Pol2 termination is enhanced via a gain-of-function mutation, G476S, in the RNA-binding domain of an essential termination factor, Seb1. The genetic and physical evidence for gain-of-function is compelling: 1) <i>seb1-G476S</i> de-represses <i>pho1</i> and <i>tgp1</i>, both of which are subject to lncRNA-mediated transcriptional interference; 2) <2021-01-01T00:00:00Z2021 Aug2026-05-31T19:55:26.38Z2025-02-18T23:32:35.648ZS-EPMC83799843438968410.1073/pnas.2108105118