7MI2
Seb1-G476S RNA binding domain
Summary for 7MI2
Entry DOI | 10.2210/pdb7mi2/pdb |
Descriptor | Rpb7-binding protein seb1, GLYCEROL, DI(HYDROXYETHYL)ETHER, ... (4 entities in total) |
Functional Keywords | rrm, termination factor, transcription interference, rna binding protein |
Biological source | Schizosaccharomyces pombe (Fission yeast) |
Total number of polymer chains | 1 |
Total formula weight | 17251.65 |
Authors | Jacewicz, A.,Shuman, S. (deposition date: 2021-04-16, release date: 2021-07-14, Last modification date: 2023-10-18) |
Primary citation | Schwer, B.,Garg, A.,Jacewicz, A.,Shuman, S. Genetic screen for suppression of transcriptional interference identifies a gain-of-function mutation in Pol2 termination factor Seb1. Proc.Natl.Acad.Sci.USA, 118:-, 2021 Cited by PubMed Abstract: The system of long noncoding RNA (lncRNA)-mediated transcriptional interference that represses fission yeast phosphate homoeostasis gene 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) de-represses and , both of which are subject to lncRNA-mediated transcriptional interference; 2) elicits precocious lncRNA transcription termination in response to lncRNA 5'-proximal poly(A) signals; 3) derepression of is effaced by loss-of-function mutations in cleavage and polyadenylation factor (CPF) subunits and termination factor Rhn1; 4) synthetic lethality of with derepressive mutants and ∆ is rescued by CPF/Rhn1 loss-of-function alleles; and 5) elicits an upstream shift in poly(A) site preference in several messenger RNA genes. A crystal structure of the Seb1-G476S RNA-binding domain indicates potential for gain of contacts from Ser476 to RNA nucleobases. To our knowledge, this is a unique instance of a gain-of-function phenotype in a eukaryal transcription termination protein. PubMed: 34389684DOI: 10.1073/pnas.2108105118 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.4 Å) |
Structure validation
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